Is ABCA3 p.Leu960Val (c.2878T>G) pathogenic?

ABCA3 p.Leu960Val (c.2878T>G) is classified Uncertain significance in ABCA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). AlphaMissense: likely benign (0.1713); Very rare (popmax 6.85e-05%).

How common is ABCA3 p.Leu960Val (c.2878T>G) in the general population?

ABCA3 p.Leu960Val (c.2878T>G) is very rare (popmax 6.85e-05%) (gnomAD).

What do computational predictors say about ABCA3 p.Leu960Val (c.2878T>G)?

AlphaMissense predicts likely benign (score 0.1713) — an in-silico prediction, not a clinical call.

ABCA3 p.Leu960Val

c.2878T>G · VCV4761950

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1713 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1713	likely benign
REVEL	0.539	indeterminate
SaProt	LLR -6.86	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 -0.013	GERP -4.9, phastCons 0.025
Regional constraint	o/e 0.98	unconstrained · MANE · 40 kb · p 0.47 · regional, not allelic
Overall
CADD	13.35	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 6.85e-05%

Overall 6.85e-05% 1/1,459,250 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: ABCA3
Protein: p.Leu960Val
Coding: c.2878T>G
MANE Select: NM_001089
Type: single nucleotide variant
Location: chr16:2288152 (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.Leu960Phe Conflicting classifications of pathogenicity ★ same residue
ABCA3 p.Leu960Ser 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

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-leu960val (accessed [today's date]).

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