Is ABCA6 p.Pro1360His (c.4079C>A) pathogenic?

ABCA6 p.Pro1360His (c.4079C>A) is classified Uncertain significance in ABCA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: ambiguous (0.3715); Ultra-rare (popmax 0.0647%, eas).

How common is ABCA6 p.Pro1360His (c.4079C>A) in the general population?

ABCA6 p.Pro1360His (c.4079C>A) is ultra-rare (popmax 0.0647%, eas) (gnomAD).

What do computational predictors say about ABCA6 p.Pro1360His (c.4079C>A)?

AlphaMissense predicts ambiguous (score 0.3715) — an in-silico prediction, not a clinical call.

ABCA6 p.Pro1360His

c.4079C>A · rs188158113 · VCV3108050

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3715 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0647%, eas)

Computational evidence

Protein change
AlphaMissense	0.3715	ambiguous
REVEL	0.512	indeterminate
SaProt	LLR -11.63	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 62 kb · p 0.14 · regional, not allelic
Overall
CADD	28.5	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 0.0647% East Asian · 29/44,830 alleles

Filtering AF 0.0462% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.04%

Overall 0.00347% 56/1,612,792 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0647%	1,546
Remaining individualsnot grpmax-eligible	0.0384%	2,602
Admixed American	0.00334%	29,896
European (non-Finnish)	8.48e-05%	1,179,458

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.Pro1360His
Coding: c.4079C>A
MANE Select: NM_080284
dbSNP: rs188158113
Type: single nucleotide variant
Location: chr17:69085133 (GRCh38)
Gene constraint: LOEUF 1.041 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.38
Residue 1360: the abc transporter 2 domain

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

Similar variants

ABCA6 p.Pro1360Ala Uncertain significance ★ ⚠ same residue
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

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-pro1360his (accessed [today's date]).

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