Is DOLK p.Ser305Pro (c.913T>C) pathogenic?

DOLK p.Ser305Pro (c.913T>C) is classified Uncertain significance in DOLK (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-13). AlphaMissense: likely pathogenic (0.737); Absent from gnomAD v4.1.

How common is DOLK p.Ser305Pro (c.913T>C) in the general population?

DOLK p.Ser305Pro (c.913T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOLK p.Ser305Pro (c.913T>C)?

AlphaMissense predicts likely pathogenic (score 0.737) — an in-silico prediction, not a clinical call.

DOLK p.Ser305Pro

c.913T>C · VCV3365015

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.737 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.737	likely pathogenic
REVEL	0.528	indeterminate
SaProt	LLR -10.77	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 1,613 bp · p 0.00089 · regional, not allelic
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: DOLK
Protein: p.Ser305Pro
Coding: c.913T>C
MANE Select: NM_014908
Type: single nucleotide variant
Location: chr9:128946391 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.37

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

Similar variants

DOLK p.Ser305Cys Uncertain significance ★★ ⚠ same residue
DOLK p.Ser305= Likely benign ★ same residue
DOLK p.His408Asp Pathogenic/Likely pathogenic ★★ same type
DOLK p.Met1Ile Pathogenic/Likely pathogenic ★★ same type
DOLK p.Met1Thr Pathogenic/Likely pathogenic ★★ same type
DOLK c.-194G>T Uncertain significance ★★ same type
DOLK c.-22G>A Uncertain significance ★★ same type
DOLK c.-269G>T 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/dolk-p-ser305pro (accessed [today's date]).

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