Is ANKMY1 p.Glu438Val (c.1313A>T) pathogenic?

ANKMY1 p.Glu438Val (c.1313A>T) is classified Uncertain significance in ANKMY1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: likely pathogenic (0.6494); Very rare (popmax 0.00167%, amr).

How common is ANKMY1 p.Glu438Val (c.1313A>T) in the general population?

ANKMY1 p.Glu438Val (c.1313A>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ANKMY1 p.Glu438Val (c.1313A>T)?

AlphaMissense predicts likely pathogenic (score 0.6494) — an in-silico prediction, not a clinical call.

ANKMY1 p.Glu438Val

c.1313A>T · VCV3296094

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6494 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6494	likely pathogenic
REVEL	0.377	indeterminate
SaProt	LLR -2.44	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 78 kb · p 0.63 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E349V vs ClinVar E438V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,980 alleles

Overall 0.000186% 3/1,613,932 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,980
South Asian	0.0011%	91,078
European (non-Finnish)	8.47e-05%	1,180,013

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: ANKMY1
Protein: p.Glu438Val
Coding: c.1313A>T
MANE Select: NM_001282771
Type: single nucleotide variant
Location: chr2:240525707 (GRCh38)
Gene constraint: LOEUF 1.141 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.09

Full ANKMY1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKMY1 p.Ala219= Benign ★★ same type
ANKMY1 p.His268Asn Likely benign ★★ same type
ANKMY1 p.Ser212Thr Benign ★★ same type
ANKMY1 p.Ala1014Gly Uncertain significance ★ ⚠ same type
ANKMY1 p.Ala165Val Uncertain significance ★ ⚠ same type
ANKMY1 p.Ala281Ser Uncertain significance ★ ⚠ same type
ANKMY1 p.Ala340Val Uncertain significance ★ ⚠ same type
ANKMY1 p.Ala356Val 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/ankmy1-p-glu438val (accessed [today's date]).

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