Is ANKMY1 p.Arg985Cys (c.2953C>T) pathogenic?

ANKMY1 p.Arg985Cys (c.2953C>T) is classified Uncertain significance in ANKMY1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). AlphaMissense: ambiguous (0.4233); Ultra-rare (popmax 0.0156%, eas).

How common is ANKMY1 p.Arg985Cys (c.2953C>T) in the general population?

ANKMY1 p.Arg985Cys (c.2953C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about ANKMY1 p.Arg985Cys (c.2953C>T)?

AlphaMissense predicts ambiguous (score 0.4233) — an in-silico prediction, not a clinical call.

ANKMY1 p.Arg985Cys

c.2953C>T · VCV3542673

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4233 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Computational evidence

Protein change
AlphaMissense	0.4233	ambiguous
REVEL	0.425	indeterminate
SaProt	LLR -9.74	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 78 kb · p 0.63 · regional, not allelic
Overall
CADD	28.9	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 R896C vs ClinVar R985C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,874 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00124% 20/1,613,998 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,411
Remaining individualsnot grpmax-eligible	0.0032%	31,251
African / African-American	0.00133%	75,064
South Asian	0.0011%	91,068
European (non-Finnish)	0.000763%	131,100

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.Arg985Cys
Coding: c.2953C>T
MANE Select: NM_001282771
Type: single nucleotide variant
Location: chr2:240481030 (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-arg985cys (accessed [today's date]).

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