Is ABCA6 p.Leu1024Pro (c.3071T>C) pathogenic?

ABCA6 p.Leu1024Pro (c.3071T>C) is classified Uncertain significance in ABCA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). AlphaMissense: likely benign (0.3107); Very rare (popmax 0.00224%, eas).

How common is ABCA6 p.Leu1024Pro (c.3071T>C) in the general population?

ABCA6 p.Leu1024Pro (c.3071T>C) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about ABCA6 p.Leu1024Pro (c.3071T>C)?

AlphaMissense predicts likely benign (score 0.3107) — an in-silico prediction, not a clinical call.

ABCA6 p.Leu1024Pro

c.3071T>C · VCV3961390

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3107 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3107	likely benign
REVEL	0.586	indeterminate
SaProt	LLR -12.29	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 -0.38	GERP -3.8
Regional constraint	o/e 1.03	unconstrained · MANE · 62 kb · p 0.14 · regional, not allelic
Overall
CADD	12.97	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 0.00224% East Asian · 1/44,730 alleles

Overall 0.000656% 1/152,326 alleles · very rare

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.Leu1024Pro
Coding: c.3071T>C
MANE Select: NM_080284
Type: single nucleotide variant
Location: chr17:69097969 (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-leu1024pro (accessed [today's date]).

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