Is ANKRD65 p.Pro36Ser (c.106C>T) pathogenic?

ANKRD65 p.Pro36Ser (c.106C>T) is classified Uncertain significance in ANKRD65 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-16). AlphaMissense: likely benign (0.107); Absent from gnomAD v4.1.

How common is ANKRD65 p.Pro36Ser (c.106C>T) in the general population?

ANKRD65 p.Pro36Ser (c.106C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD65 p.Pro36Ser (c.106C>T)?

AlphaMissense predicts likely benign (score 0.107) — an in-silico prediction, not a clinical call.

ANKRD65 p.Pro36Ser

c.106C>T · rs2523661780 · VCV2336146

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.107 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.107	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -6.83	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 -0.14	GERP -1.8
Regional constraint	o/e 1.15	unconstrained · MANE · 1,902 bp · p 0.00072 · regional, not allelic
Overall
CADD	10.38	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANKRD65
Protein: p.Pro36Ser
Coding: c.106C>T
MANE Select: NM_001145210
dbSNP: rs2523661780
Type: single nucleotide variant
Location: chr1:1420900 (GRCh38)
Gene constraint: LOEUF 1.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.07

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-pro36ser (accessed [today's date]).

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