Is ABCA2 p.Gly1676Ser (c.5026G>A) pathogenic?

ABCA2 p.Gly1676Ser (c.5026G>A) is classified Uncertain significance in ABCA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-18). AlphaMissense: likely benign (0.1399); Rare (popmax 0.809%, eas); Associated with intellectual developmental disorder with poor growth and with or without seizures or ataxia.

How common is ABCA2 p.Gly1676Ser (c.5026G>A) in the general population?

ABCA2 p.Gly1676Ser (c.5026G>A) is rare (popmax 0.809%, eas) (gnomAD).

What do computational predictors say about ABCA2 p.Gly1676Ser (c.5026G>A)?

AlphaMissense predicts likely benign (score 0.1399) — an in-silico prediction, not a clinical call.

ABCA2 p.Gly1676Ser

Q: What condition is associated with ABCA2 p.Gly1676Ser (c.5026G>A)?

ABCA2 p.Gly1676Ser (c.5026G>A) is associated with intellectual developmental disorder with poor growth and with or without seizures or ataxia (ClinVar).

c.5026G>A · rs184422644 · VCV1325502

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1399 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.809%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.1399	likely benign
REVEL	0.621	indeterminate
SaProt	LLR -8.48	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 3,800 bp · p 6.1e-23 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM G1675S vs ClinVar G1676S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.809% East Asian · 363/44,864 alleles

Filtering AF 0.741% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.714%

Overall 0.0351% 566/1,612,638 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.809%	124
South Asian	0.135%	741
African / African-American	0.0386%	2,588
Remaining individualsnot grpmax-eligible	0.0368%	2,716
Middle Eastern	0.0165%	6,048
Admixed American	0.00333%	30,009
European (non-Finnish)	0.00212%	47,196

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.Gly1676Ser
Coding: c.5026G>A
MANE Select: NM_001606
dbSNP: rs184422644
Type: single nucleotide variant
Location: chr9:137012767 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46
Residue 1676: a UniProt-annotated variant site (in idpogsa)

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-gly1676ser (accessed [today's date]).

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