Is ANKMY2 p.Val72Ala (c.215T>C) pathogenic?

ANKMY2 p.Val72Ala (c.215T>C) is classified Uncertain significance in ANKMY2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-27). AlphaMissense: likely pathogenic (0.6395); Ultra-rare (popmax 0.0573%, afr).

How common is ANKMY2 p.Val72Ala (c.215T>C) in the general population?

ANKMY2 p.Val72Ala (c.215T>C) is ultra-rare (popmax 0.0573%, afr) (gnomAD).

What do computational predictors say about ANKMY2 p.Val72Ala (c.215T>C)?

AlphaMissense predicts likely pathogenic (score 0.6395) — an in-silico prediction, not a clinical call.

ANKMY2 p.Val72Ala

c.215T>C · rs138973925 · VCV2375967

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6395 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0573%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6395	likely pathogenic
REVEL	0.171	moderately benign-leaning
SaProt	LLR -8.55	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 5.3, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 45 kb · p 0.073 · regional, not allelic
Overall
CADD	23.0	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 0.0573% African / African-American · 43/75,048 alleles

Filtering AF 0.0436% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0389%

Overall 0.00335% 54/1,612,932 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0573%	1,745
Admixed American	0.015%	6,648
East Asian	0.00223%	44,776
Remaining individualsnot grpmax-eligible	0.0016%	62,450

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: ANKMY2
Protein: p.Val72Ala
Coding: c.215T>C
MANE Select: NM_020319
dbSNP: rs138973925
Type: single nucleotide variant
Location: chr7:16627096 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.89

Full ANKMY2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKMY2 p.Ala161Val Uncertain significance ★ ⚠ same type
ANKMY2 p.Ala279Ser Uncertain significance ★ ⚠ same type
ANKMY2 p.Ala300Val Uncertain significance ★ ⚠ same type
ANKMY2 p.Arg254Gly Uncertain significance ★ ⚠ same type
ANKMY2 p.Asn110His Uncertain significance ★ ⚠ same type
ANKMY2 p.Asn134Ser Uncertain significance ★ ⚠ same type
ANKMY2 p.Asp316Tyr Uncertain significance ★ ⚠ same type
ANKMY2 p.Asp71Gly 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/ankmy2-p-val72ala (accessed [today's date]).

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