Is ANKRD63 p.Ser294Pro (c.880T>C) pathogenic?

ANKRD63 p.Ser294Pro (c.880T>C) is classified Uncertain significance in ANKRD63 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-25). AlphaMissense: likely benign (0.0978); No allele count reported in gnomAD v4.1 (AN 1,534,708).

How common is ANKRD63 p.Ser294Pro (c.880T>C) in the general population?

ANKRD63 p.Ser294Pro (c.880T>C) is no allele count reported in gnomAD v4.1 (AN 1,534,708) (gnomAD).

What do computational predictors say about ANKRD63 p.Ser294Pro (c.880T>C)?

AlphaMissense predicts likely benign (score 0.0978) — an in-silico prediction, not a clinical call.

ANKRD63 p.Ser294Pro

c.880T>C · VCV4108572

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0978 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,534,708)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0978	likely benign
REVEL	0.221	benign-leaning
SaProt	LLR -8.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.1, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 592 bp · p 0.3 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,534,708). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ANKRD63
Protein: p.Ser294Pro
Coding: c.880T>C
MANE Select: NM_001190479
Type: single nucleotide variant
Location: chr15:40281707 (GRCh38)
Gene constraint: LOEUF 1.835 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.92
Residue 294: a modified residue (phosphoserine)

Full ANKRD63 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD63 p.Ala163Thr Uncertain significance ★ ⚠ same type
ANKRD63 p.Ala182Thr Uncertain significance ★ ⚠ same type
ANKRD63 p.Ala201Glu Uncertain significance ★ ⚠ same type
ANKRD63 p.Ala201Thr Uncertain significance ★ ⚠ same type
ANKRD63 p.Ala226Thr Uncertain significance ★ ⚠ same type
ANKRD63 p.Ala236Thr Uncertain significance ★ ⚠ same type
ANKRD63 p.Ala269Val Uncertain significance ★ ⚠ same type
ANKRD63 p.Ala276Ser 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/ankrd63-p-ser294pro (accessed [today's date]).

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