Is ABCA6 p.Arg427Cys (c.1279C>T) pathogenic?

ABCA6 p.Arg427Cys (c.1279C>T) is classified Uncertain significance in ABCA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-08). AlphaMissense: likely benign (0.0679); Ultra-rare (popmax 0.0294%, eas).

How common is ABCA6 p.Arg427Cys (c.1279C>T) in the general population?

ABCA6 p.Arg427Cys (c.1279C>T) is ultra-rare (popmax 0.0294%, eas) (gnomAD).

What do computational predictors say about ABCA6 p.Arg427Cys (c.1279C>T)?

AlphaMissense predicts likely benign (score 0.0679) — an in-silico prediction, not a clinical call.

ABCA6 p.Arg427Cys

c.1279C>T · VCV3960368

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0679 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0294%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0679	likely benign
REVEL	0.149	moderately benign-leaning
SaProt	LLR -8.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.27	acceptor loss · deltas
Constraint at this position
Conservation	phyloP -0.63	GERP -2
Regional constraint	o/e 1.03	unconstrained · MANE · 62 kb · p 0.14 · regional, not allelic
Overall
CADD	10.12	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 0.0294% East Asian · 12/40,810 alleles

Filtering AF 0.018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.015%

Overall 0.00296% 44/1,485,306 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0294%	3,401
South Asian	0.0276%	3,625
Remaining individualsnot grpmax-eligible	0.00358%	27,918
European (non-Finnish)	0.000997%	100,337

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.Arg427Cys
Coding: c.1279C>T
MANE Select: NM_080284
Type: single nucleotide variant
Location: chr17:69123396 (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.Arg427Gly Uncertain significance ★ ⚠ same residue
ABCA6 p.Arg427His 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-arg427cys (accessed [today's date]).

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