Is ANKRD63 p.Pro4His (c.11C>A) pathogenic?

ANKRD63 p.Pro4His (c.11C>A) is classified Uncertain significance in ANKRD63 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely pathogenic (0.9568); No allele count reported in gnomAD v4.1 (AN 1,426,938).

How common is ANKRD63 p.Pro4His (c.11C>A) in the general population?

ANKRD63 p.Pro4His (c.11C>A) is no allele count reported in gnomAD v4.1 (AN 1,426,938) (gnomAD).

What do computational predictors say about ANKRD63 p.Pro4His (c.11C>A)?

AlphaMissense predicts likely pathogenic (score 0.9568) — an in-silico prediction, not a clinical call.

ANKRD63 p.Pro4His

c.11C>A · VCV4108584

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9568 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,426,938)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9568	likely pathogenic · top 10% in ANKRD63
REVEL	0.086	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 12	GERP 1.3, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 546 bp · p 9.3e-05 · regional, not allelic
Overall
CADD	25.6	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

No allele count reported in gnomAD v4.1 (AN 1,426,938). 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.Pro4His
Coding: c.11C>A
MANE Select: NM_001190479
Type: single nucleotide variant
Location: chr15:40282576 (GRCh38)
Gene constraint: LOEUF 1.835 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.92

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-pro4his (accessed [today's date]).

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