Is ABCA3 p.Val337Met (c.1009G>A) pathogenic?

ABCA3 p.Val337Met (c.1009G>A) is classified Uncertain significance in ABCA3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-19). AlphaMissense: likely pathogenic (0.6177); Very rare (popmax 0.00891%, eas).

How common is ABCA3 p.Val337Met (c.1009G>A) in the general population?

ABCA3 p.Val337Met (c.1009G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about ABCA3 p.Val337Met (c.1009G>A)?

AlphaMissense predicts likely pathogenic (score 0.6177) — an in-silico prediction, not a clinical call.

ABCA3 p.Val337Met

c.1009G>A · rs764506198 · VCV1708362

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6177 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6177	likely pathogenic
REVEL	0.584	indeterminate
SaProt	LLR -5.74	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 40 kb · p 0.47 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,880 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00118% 19/1,613,740 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,220
South Asian	0.0022%	45,538
Admixed American	0.00167%	59,994
Finnishnot grpmax-eligible	0.00157%	63,782
European (non-Finnish)	0.000932%	107,275

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: ABCA3
Protein: p.Val337Met
Coding: c.1009G>A
MANE Select: NM_001089
dbSNP: rs764506198
Type: single nucleotide variant
Location: chr16:2317385 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB
Residue 337: a β-strand

Full ABCA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA3 p.Val337= Likely benign ★★ same residue
ABCA3 c.1112-20G>A Likely pathogenic ★★ same type
ABCA3 c.2053-1G>C Likely pathogenic ★★ same type
ABCA3 c.2414+1G>A Likely pathogenic ★★ same type
ABCA3 c.3863-98C>T Pathogenic ★★ same type
ABCA3 c.614-2A>G Likely pathogenic ★★ same type
ABCA3 p.Ala1070Thr Likely pathogenic ★★ ⚠ same type
ABCA3 p.Arg1550Trp Likely pathogenic ★★ 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/abca3-p-val337met (accessed [today's date]).

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