Is ABCA6 p.Arg427His (c.1280G>A) pathogenic?

ABCA6 p.Arg427His (c.1280G>A) is classified Uncertain significance in ABCA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-20). AlphaMissense: likely benign (0.0578); Rare (popmax 0.142%, sas).

How common is ABCA6 p.Arg427His (c.1280G>A) in the general population?

ABCA6 p.Arg427His (c.1280G>A) is rare (popmax 0.142%, sas) (gnomAD).

What do computational predictors say about ABCA6 p.Arg427His (c.1280G>A)?

AlphaMissense predicts likely benign (score 0.0578) — an in-silico prediction, not a clinical call.

ABCA6 p.Arg427His

c.1280G>A · rs745521265 · VCV3106320

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0578 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.142%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0578	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -7.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP -5.4	GERP -5
Regional constraint	o/e 1.03	unconstrained · MANE · 62 kb · p 0.14 · regional, not allelic
Overall
CADD	0.26	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 0.142% South Asian · 98/68,956 alleles

Filtering AF 0.119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.111%

Overall 0.007% 104/1,485,412 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.142%	704
Remaining individualsnot grpmax-eligible	0.00358%	27,952
African / African-American	0.0014%	71,278
European (non-Finnish)	0.000272%	367,920

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.Arg427His
Coding: c.1280G>A
MANE Select: NM_080284
dbSNP: rs745521265
Type: single nucleotide variant
Location: chr17:69123395 (GRCh38)
Gene constraint: LOEUF 1.041 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.38

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

Similar variants

ABCA6 p.Arg427Cys Uncertain significance ★ ⚠ same residue
ABCA6 p.Arg427Gly 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

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-arg427his (accessed [today's date]).

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