Is ABCA6 p.Arg844His (c.2531G>A) pathogenic?

ABCA6 p.Arg844His (c.2531G>A) is classified Uncertain significance in ABCA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: likely benign (0.117); Ultra-rare (popmax 0.0165%, sas).

How common is ABCA6 p.Arg844His (c.2531G>A) in the general population?

ABCA6 p.Arg844His (c.2531G>A) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

What do computational predictors say about ABCA6 p.Arg844His (c.2531G>A)?

AlphaMissense predicts likely benign (score 0.117) — an in-silico prediction, not a clinical call.

ABCA6 p.Arg844His

c.2531G>A · rs376370716 · VCV2368877

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.117 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.117	likely benign
REVEL	0.306	indeterminate
SaProt	LLR -10.56	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.82	GERP -0.96, phastCons 0.26
Regional constraint	o/e 1.03	unconstrained · MANE · 62 kb · p 0.14 · regional, not allelic
Overall
CADD	19.88	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 0.0165% South Asian · 15/90,812 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00823%

Overall 0.00484% 78/1,612,978 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0165%	6,054
Middle Eastern	0.0165%	6,056
Remaining individualsnot grpmax-eligible	0.0112%	8,925
East Asian	0.0111%	8,970
African / African-American	0.008%	12,496
Finnishnot grpmax-eligible	0.00469%	21,331
Admixed American	0.00334%	29,928
European (non-Finnish)	0.00331%	30,242

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.Arg844His
Coding: c.2531G>A
MANE Select: NM_080284
dbSNP: rs376370716
Type: single nucleotide variant
Location: chr17:69106070 (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.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-arg844his (accessed [today's date]).

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