Is ANKRD65 p.Pro383Ser (c.1147C>T) pathogenic?

ANKRD65 p.Pro383Ser (c.1147C>T) is classified Uncertain significance in ANKRD65 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-07). AlphaMissense: likely benign (0.1095); Very rare (popmax 0.00228%, nfe).

How common is ANKRD65 p.Pro383Ser (c.1147C>T) in the general population?

ANKRD65 p.Pro383Ser (c.1147C>T) is very rare (popmax 0.00228%, nfe) (gnomAD).

What do computational predictors say about ANKRD65 p.Pro383Ser (c.1147C>T)?

AlphaMissense predicts likely benign (score 0.1095) — an in-silico prediction, not a clinical call.

ANKRD65 p.Pro383Ser

c.1147C>T · rs921851814 · VCV2481928

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1095 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00228%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1095	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -7.17	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 0.83	GERP -1.8, phastCons 0.23
Regional constraint	o/e 1.15	unconstrained · MANE · 1,902 bp · p 0.00072 · regional, not allelic
Overall
CADD	5.583	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 0.00228% European (non-Finnish) · 26/1,138,312 alleles

Filtering AF 0.00159% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00169% 26/1,539,060 alleles · very rare exomes 25/1,386,830 · genomes 1/152,230 · 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: ANKRD65
Protein: p.Pro383Ser
Coding: c.1147C>T
MANE Select: NM_001145210
dbSNP: rs921851814
Type: single nucleotide variant
Location: chr1:1419153 (GRCh38)
Gene constraint: LOEUF 1.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.07
Residue 383: the 'disordered' region

Full ANKRD65 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD65 p.Ala106Val Uncertain significance ★ ⚠ same type
ANKRD65 p.Ala115Thr Uncertain significance ★ ⚠ same type
ANKRD65 p.Ala147Asp Uncertain significance ★ ⚠ same type
ANKRD65 p.Ala162Pro Uncertain significance ★ ⚠ same type
ANKRD65 p.Ala168Thr Uncertain significance ★ ⚠ same type
ANKRD65 p.Ala170Val Uncertain significance ★ ⚠ same type
ANKRD65 p.Ala180Val Uncertain significance ★ ⚠ same type
ANKRD65 p.Ala198Ser 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/ankrd65-p-pro383ser (accessed [today's date]).

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