Is ANK1 p.Val1007Met (c.3019G>A) pathogenic?

ANK1 p.Val1007Met (c.3019G>A) is classified Likely benign in ANK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). AlphaMissense: ambiguous (0.3728); Ultra-rare (popmax 0.0253%, sas); Associated with hereditary spherocytosis type 1.

What condition is associated with ANK1 p.Val1007Met (c.3019G>A)?

ANK1 p.Val1007Met (c.3019G>A) is associated with hereditary spherocytosis type 1 (ClinVar).

How common is ANK1 p.Val1007Met (c.3019G>A) in the general population?

ANK1 p.Val1007Met (c.3019G>A) is ultra-rare (popmax 0.0253%, sas) (gnomAD).

How is Hereditary spherocytosis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ANK1 p.Val1007Met (c.3019G>A)?

AlphaMissense predicts ambiguous (score 0.3728) — an in-silico prediction, not a clinical call.

ANK1 p.Val1007Met

c.3019G>A · rs202226361 · VCV2439059

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3728 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, sas)

Conditions

hereditary spherocytosis type 1

Computational evidence

Protein change
AlphaMissense	0.3728	ambiguous
REVEL	0.43	indeterminate
SaProt	LLR -9.74	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 38 kb · p 1e-12 · regional, not allelic
Overall
CADD	25.7	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 0.0253% South Asian · 23/91,080 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0201%

Overall 0.0379% 612/1,614,090 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.464%	215
Amishnot grpmax-eligible	0.219%	456
South Asiangrpmax	0.0253%	3,960
European (non-Finnish)	0.0233%	4,291
Remaining individualsnot grpmax-eligible	0.0192%	5,209
Admixed American	0.00333%	30,016
African / African-American	0.00133%	75,040

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val1007Met
Coding: c.3019G>A
MANE Select: NM_000037
dbSNP: rs202226361
Type: single nucleotide variant
Location: chr8:41695273 (GRCh38)
Gene constraint: LOEUF 0.299 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.64 · 21 PDB
Residue 1007: a β-strand; the zu5 1 domain

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

Disease context

hereditary spherocytosis type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary spherocytosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages
Prevalence: 1-5 / 10 000 (Germany)

Similar variants

ANK1 c.1305+1G>A Pathogenic ★★ same condition
ANK1 c.1405-9G>A Pathogenic/Likely pathogenic ★★ same condition
ANK1 c.1702-2A>G Pathogenic/Likely pathogenic ★★ same condition
ANK1 c.1801-17G>A Pathogenic/Likely pathogenic ★★ same condition
ANK1 c.2296-1G>A Likely pathogenic ★★ same condition
ANK1 c.2296-2A>G Pathogenic/Likely pathogenic ★★ same condition
ANK1 c.2389-2A>G Likely pathogenic ★★ same condition
ANK1 c.2462-2A>G Pathogenic ★★ 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-val1007met (accessed [today's date]).

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