Is ANKRD63 p.Pro284Ser (c.850C>T) pathogenic?

ANKRD63 p.Pro284Ser (c.850C>T) is classified Uncertain significance in ANKRD63 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-11). AlphaMissense: likely benign (0.0894); Very rare (popmax 8.72e-05%, nfe).

How common is ANKRD63 p.Pro284Ser (c.850C>T) in the general population?

ANKRD63 p.Pro284Ser (c.850C>T) is very rare (popmax 8.72e-05%, nfe) (gnomAD).

What do computational predictors say about ANKRD63 p.Pro284Ser (c.850C>T)?

AlphaMissense predicts likely benign (score 0.0894) — an in-silico prediction, not a clinical call.

ANKRD63 p.Pro284Ser

c.850C>T · VCV4860090

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0894 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.72e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0894	likely benign
REVEL	0.129	moderately benign-leaning
SaProt	LLR -6.20	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 9.9	GERP 0.95, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 592 bp · p 0.3 · regional, not allelic
Overall
CADD	25.1	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

Grpmax group 8.72e-05% European (non-Finnish) · 1/1,146,560 alleles

Overall 6.51e-05% 1/1,535,158 alleles · very rare exomes 1/1,382,796 · genomes 0/152,362 · joint denominator

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: ANKRD63
Protein: p.Pro284Ser
Coding: c.850C>T
MANE Select: NM_001190479
Type: single nucleotide variant
Location: chr15:40281737 (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-pro284ser (accessed [today's date]).

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