Is ABCA6 p.Ala1387Val (c.4160C>T) pathogenic?

ABCA6 p.Ala1387Val (c.4160C>T) is classified Likely benign in ABCA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-26). AlphaMissense: likely benign (0.0935); Ultra-rare (popmax 0.0762%, sas).

How common is ABCA6 p.Ala1387Val (c.4160C>T) in the general population?

ABCA6 p.Ala1387Val (c.4160C>T) is ultra-rare (popmax 0.0762%, sas) (gnomAD).

What do computational predictors say about ABCA6 p.Ala1387Val (c.4160C>T)?

AlphaMissense predicts likely benign (score 0.0935) — an in-silico prediction, not a clinical call.

ABCA6 p.Ala1387Val

c.4160C>T · rs527461596 · VCV2374946

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0935 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0762%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0935	likely benign
REVEL	0.296	indeterminate
SaProt	LLR -6.81	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 -3.2	GERP -3.8
Regional constraint	o/e 1.03	unconstrained · MANE · 62 kb · p 0.14 · regional, not allelic
Overall
CADD	0.003	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 0.0762% South Asian · 69/90,508 alleles

Filtering AF 0.0617% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0564%

Overall 0.00528% 85/1,610,584 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0762%	1,312
Remaining individualsnot grpmax-eligible	0.0128%	7,792
East Asian	0.00223%	44,780
Admixed American	0.00171%	58,648
European (non-Finnish)	0.000509%	196,537

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: ABCA6
Protein: p.Ala1387Val
Coding: c.4160C>T
MANE Select: NM_080284
dbSNP: rs527461596
Type: single nucleotide variant
Location: chr17:69085052 (GRCh38)
Gene constraint: LOEUF 1.041 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.38
Residue 1387: the abc transporter 2 domain

Full ABCA6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA6 p.Ala1043Gly Uncertain significance ★ ⚠ same type
ABCA6 p.Ala107Thr Uncertain significance ★ ⚠ same type
ABCA6 p.Ala1287Thr Uncertain significance ★ ⚠ same type
ABCA6 p.Ala1303Thr Uncertain significance ★ ⚠ same type
ABCA6 p.Ala1389Glu Uncertain significance ★ ⚠ same type
ABCA6 p.Ala1392Thr Uncertain significance ★ ⚠ same type
ABCA6 p.Ala1454Thr Uncertain significance ★ ⚠ same type
ABCA6 p.Ala1535Val Uncertain significance ★ ⚠ 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/abca6-p-ala1387val (accessed [today's date]).

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