Is ABCA3 p.Pro1301Ser (c.3901C>T) pathogenic?

ABCA3 p.Pro1301Ser (c.3901C>T) is classified Uncertain significance in ABCA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-31). AlphaMissense: likely benign (0.2645); Very rare (popmax 6.85e-05%).

How common is ABCA3 p.Pro1301Ser (c.3901C>T) in the general population?

ABCA3 p.Pro1301Ser (c.3901C>T) is very rare (popmax 6.85e-05%) (gnomAD).

What do computational predictors say about ABCA3 p.Pro1301Ser (c.3901C>T)?

AlphaMissense predicts likely benign (score 0.2645) — an in-silico prediction, not a clinical call.

ABCA3 p.Pro1301Ser

c.3901C>T · VCV4736512

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2645 · 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	0.2645	likely benign
REVEL	0.508	indeterminate
SaProt	LLR -6.36	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 12	GERP 1.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 10 kb · p 0.0034 · regional, not allelic
Overall
CADD	22.8	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% 1/1,460,886 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.Pro1301Ser
Coding: c.3901C>T
MANE Select: NM_001089
Type: single nucleotide variant
Location: chr16:2283320 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB
Residue 1301: a β-strand; a UniProt-annotated variant site (in smdp3)

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

Similar variants

ABCA3 p.Pro1301= Likely benign ★★ same residue
ABCA3 p.Pro1301Arg 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-pro1301ser (accessed [today's date]).

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