Is ANK1 p.Ala510Val (c.1529C>T) pathogenic?

ANK1 p.Ala510Val (c.1529C>T) is classified Uncertain significance in ANK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-08). AlphaMissense: likely benign (0.2237); Ultra-rare (popmax 0.033%, mid); Associated with Inborn genetic diseases.

What condition is associated with ANK1 p.Ala510Val (c.1529C>T)?

ANK1 p.Ala510Val (c.1529C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ANK1 p.Ala510Val (c.1529C>T) in the general population?

ANK1 p.Ala510Val (c.1529C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about ANK1 p.Ala510Val (c.1529C>T)?

AlphaMissense predicts likely benign (score 0.2237) — an in-silico prediction, not a clinical call.

ANK1 p.Ala510Val

c.1529C>T · VCV3538706

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2237 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2237	likely benign
REVEL	0.59	indeterminate
SaProt	LLR -13.70	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 9.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 38 kb · p 1e-12 · regional, not allelic
Overall
CADD	24.3	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 0.033% Middle Eastern · 2/6,066 alleles

Filtering AF 0.00581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.00161% 26/1,614,122 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,033
European (non-Finnish)	0.00186%	53,639
Remaining individualsnot grpmax-eligible	0.0016%	62,488
African / African-American	0.00133%	74,940

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: ANK1
Protein: p.Ala510Val
Coding: c.1529C>T
MANE Select: NM_000037
Type: single nucleotide variant
Location: chr8:41715725 (GRCh38)
Gene constraint: LOEUF 0.299 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.64 · 21 PDB
Residue 510: an α-helix; the '89 kda domain' region

Full ANK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANK1 p.Ala1590Thr Uncertain significance ★★ ⚠ same condition
ANK1 p.Ala1659Val Uncertain significance ★★ ⚠ same condition
ANK1 p.Ala1789Thr Uncertain significance ★★ ⚠ same condition
ANK1 p.Ala329Ser Uncertain significance ★★ ⚠ same condition
ANK1 p.Ala543Val Uncertain significance ★★ ⚠ same condition
ANK1 p.Arg1148Gln Uncertain significance ★★ ⚠ same condition
ANK1 p.Arg1255His Uncertain significance ★★ ⚠ same condition
ANK1 p.Arg1319Trp Uncertain significance ★★ ⚠ same condition

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/ank1-p-ala510val (accessed [today's date]).

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