Is ANK1 p.Val577= (c.1731C>G) pathogenic?

ANK1 p.Val577= (c.1731C>G) is classified Likely benign in ANK1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-06). Ultra-rare (popmax 0.0114%, sas).

How common is ANK1 p.Val577= (c.1731C>G) in the general population?

ANK1 p.Val577= (c.1731C>G) is ultra-rare (popmax 0.0114%, sas) (gnomAD).

ANK1 p.Val577=

c.1731C>G · rs777088455 · VCV758208

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0114%, sas)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.66	GERP -4.3, phastCons 0.001
Overall
CADD	3.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0114% South Asian · 9/79,154 alleles

Filtering AF 0.00583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00436%

Overall 0.0013% 20/1,540,608 alleles · ultra-rare exomes 18/1,388,430 · genomes 2/152,178 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0114%	8,795
Remaining individualsnot grpmax-eligible	0.00682%	14,653
African / African-American	0.00136%	73,532
European (non-Finnish)	0.000529%	189,092

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.Val577=
Coding: c.1731C>G
MANE Select: NM_000037
dbSNP: rs777088455
Type: single nucleotide variant
Location: chr8:41714225 (GRCh38)

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

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-val577 (accessed [today's date]).

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