Is ANKRD12 p.Arg956Ser (c.2868G>T) pathogenic?

ANKRD12 p.Arg956Ser (c.2868G>T) is classified Uncertain significance in ANKRD12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-19). AlphaMissense: ambiguous (0.5637); Very rare (popmax 0.000947%, nfe).

How common is ANKRD12 p.Arg956Ser (c.2868G>T) in the general population?

ANKRD12 p.Arg956Ser (c.2868G>T) is very rare (popmax 0.000947%, nfe) (gnomAD).

What do computational predictors say about ANKRD12 p.Arg956Ser (c.2868G>T)?

AlphaMissense predicts ambiguous (score 0.5637) — an in-silico prediction, not a clinical call.

ANKRD12 p.Arg956Ser

c.2868G>T · VCV3866799

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5637 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000947%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5637	ambiguous
REVEL	0.057	moderately benign-leaning
SaProt	LLR -7.76	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.062	GERP -3.2, phastCons 0.12
Regional constraint	o/e 1.15	unconstrained · MANE · 37 kb · p 6.1e-10 · regional, not allelic
Overall
CADD	11.85	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 0.000947% European (non-Finnish) · 11/1,161,016 alleles

Filtering AF 0.000508% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000372%

Overall 0.000784% 11/1,403,680 alleles · very rare

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: ANKRD12
Protein: p.Arg956Ser
Coding: c.2868G>T
MANE Select: NM_015208
Type: single nucleotide variant
Location: chr18:9256135 (GRCh38)
Gene constraint: LOEUF 0.583 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 41.33
Residue 956: the 'disordered' region

Full ANKRD12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD12 p.Ala1049Thr Uncertain significance ★ ⚠ same type
ANKRD12 p.Ala1393Val Uncertain significance ★ ⚠ same type
ANKRD12 p.Ala1479Val Uncertain significance ★ ⚠ same type
ANKRD12 p.Ala1572Val Uncertain significance ★ ⚠ same type
ANKRD12 p.Ala1752Gly Uncertain significance ★ ⚠ same type
ANKRD12 p.Ala1805Thr Uncertain significance ★ ⚠ same type
ANKRD12 p.Ala1814Glu Uncertain significance ★ ⚠ same type
ANKRD12 p.Ala2013Val 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/ankrd12-p-arg956ser (accessed [today's date]).

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