Is ABCA5 p.Ser230Ala (c.688T>G) pathogenic?

ABCA5 p.Ser230Ala (c.688T>G) is classified Uncertain significance in ABCA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-10). AlphaMissense: likely benign (0.1488); Very rare (popmax 0.000597%, nfe).

How common is ABCA5 p.Ser230Ala (c.688T>G) in the general population?

ABCA5 p.Ser230Ala (c.688T>G) is very rare (popmax 0.000597%, nfe) (gnomAD).

What do computational predictors say about ABCA5 p.Ser230Ala (c.688T>G)?

AlphaMissense predicts likely benign (score 0.1488) — an in-silico prediction, not a clinical call.

ABCA5 p.Ser230Ala

c.688T>G · VCV3853072

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1488 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000597%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1488	likely benign
REVEL	0.504	indeterminate
SaProt	LLR -6.59	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 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 67 kb · p 0.22 · regional, not allelic
Overall
CADD	23.1	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000597% European (non-Finnish) · 7/1,173,230 alleles

Filtering AF 0.000248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00016%

Overall 0.000483% 7/1,448,460 alleles · very rare

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: ABCA5
Protein: p.Ser230Ala
Coding: c.688T>G
MANE Select: NM_172232
Type: single nucleotide variant
Location: chr17:69306825 (GRCh38)
Gene constraint: LOEUF 0.97 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.12

Full ABCA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA5 p.Ser288Phe Uncertain significance ★★ ⚠ same type
ABCA5 c.4765+3A>G Likely benign ★★ same type
ABCA5 p.Asn190Ser Likely benign ★★ ⚠ same type
ABCA5 p.Asn768Asp Benign ★★ same type
ABCA5 p.Asp817Tyr Likely benign ★★ ⚠ same type
ABCA5 p.Gly1159Arg Likely benign ★★ ⚠ same type
ABCA5 p.Gly128= Benign/Likely benign ★★ same type
ABCA5 p.Ile1173Val Likely benign ★★ same type

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/abca5-p-ser230ala (accessed [today's date]).

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