Is ABCA3 p.Arg1174Trp (c.3520C>T) pathogenic?

ABCA3 p.Arg1174Trp (c.3520C>T) is classified Uncertain significance in ABCA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-03). AlphaMissense: likely benign (0.0788); Ultra-rare (popmax 0.0174%, afr).

How common is ABCA3 p.Arg1174Trp (c.3520C>T) in the general population?

ABCA3 p.Arg1174Trp (c.3520C>T) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

What do computational predictors say about ABCA3 p.Arg1174Trp (c.3520C>T)?

AlphaMissense predicts likely benign (score 0.0788) — an in-silico prediction, not a clinical call.

ABCA3 p.Arg1174Trp

c.3520C>T · rs112168649 · VCV2054826

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0788 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0788	likely benign
REVEL	0.273	benign-leaning
SaProt	LLR -6.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.45	GERP -4.8
Regional constraint	o/e 0.90	unconstrained · MANE · 10 kb · p 0.0034 · regional, not allelic
Overall
CADD	9.967	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 0.0174% African / African-American · 13/74,894 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.00297% 48/1,613,644 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,761
Remaining individualsnot grpmax-eligible	0.0128%	7,810
East Asian	0.0111%	8,975
Admixed American	0.00333%	30,000
South Asian	0.0022%	45,542
European (non-Finnish)	0.00153%	65,555

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.Arg1174Trp
Coding: c.3520C>T
MANE Select: NM_001089
dbSNP: rs112168649
Type: single nucleotide variant
Location: chr16:2284962 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB

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

Similar variants

ABCA3 p.Arg1174Gln Uncertain significance ★ 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-arg1174trp (accessed [today's date]).

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