Is ABCA2 p.Ser308Trp (c.923C>G) pathogenic?

ABCA2 p.Ser308Trp (c.923C>G) is classified Uncertain significance in ABCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-13). AlphaMissense: likely benign (0.1595); Very rare (popmax 0.00141%, afr); Associated with intellectual developmental disorder with poor growth and with or without seizures or ataxia.

How common is ABCA2 p.Ser308Trp (c.923C>G) in the general population?

ABCA2 p.Ser308Trp (c.923C>G) is very rare (popmax 0.00141%, afr) (gnomAD).

What do computational predictors say about ABCA2 p.Ser308Trp (c.923C>G)?

AlphaMissense predicts likely benign (score 0.1595) — an in-silico prediction, not a clinical call.

ABCA2 p.Ser308Trp

Q: What condition is associated with ABCA2 p.Ser308Trp (c.923C>G)?

ABCA2 p.Ser308Trp (c.923C>G) is associated with intellectual developmental disorder with poor growth and with or without seizures or ataxia (ClinVar).

c.923C>G · rs775540856 · VCV2690797

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1595 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00141%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual developmental disorder with poor growth and with or without seizures or ataxia

Computational evidence

Protein change
AlphaMissense	0.1595	likely benign
REVEL	0.238	benign-leaning
SaProt	LLR -11.41	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	GERP 1.3, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,023 bp · p 0.16 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S307W vs ClinVar S308W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00141% African / African-American · 1/70,982 alleles

Filtering AF 7.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.000451% 6/1,330,256 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00175%	57,170
African / African-Americangrpmax	0.00141%	70,982
South Asian	0.00136%	73,482
European (non-Finnish)	0.000269%	371,515

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ABCA2
Protein: p.Ser308Trp
Coding: c.923C>G
MANE Select: NM_001606
dbSNP: rs775540856
Type: single nucleotide variant
Location: chr9:137021036 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46

Full ABCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual developmental disorder with poor growth and with or without seizures or ataxia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCA2 p.Gln1370Ter Likely pathogenic ★★ same condition
ABCA2 p.Ala367Thr Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg114Gln Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg1160His Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg1383His Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg1664Trp Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg954His Uncertain significance ★★ ⚠ same condition
ABCA2 p.Asn1755Lys Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abca2-p-ser308trp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown