Is DOCK10 p.Phe993Leu (c.2977T>C) pathogenic?

DOCK10 p.Phe993Leu (c.2977T>C) is classified Uncertain significance in DOCK10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-03). AlphaMissense: likely pathogenic (0.9176); Absent from gnomAD v4.1.

How common is DOCK10 p.Phe993Leu (c.2977T>C) in the general population?

DOCK10 p.Phe993Leu (c.2977T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOCK10 p.Phe993Leu (c.2977T>C)?

AlphaMissense predicts likely pathogenic (score 0.9176) — an in-silico prediction, not a clinical call.

DOCK10 p.Phe993Leu

c.2977T>C · VCV4014067

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9176 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,532,234)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9176	likely pathogenic
REVEL	0.514	indeterminate
SaProt	LLR -8.71	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 219 kb · p 0.24 · regional, not allelic
Overall
CADD	25.2	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 1,532,234). 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: DOCK10
Protein: p.Phe993Leu
Coding: c.2977T>C
MANE Select: NM_014689
Type: single nucleotide variant
Location: chr2:224830600 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.47 · 4 PDB

Full DOCK10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK10 p.Asp2034= Benign ★★ same type
DOCK10 p.Ser1349= Benign ★★ same type
DOCK10 p.Thr1950= Benign ★★ same type
DOCK10 p.Ala112Ser Uncertain significance ★ ⚠ same type
DOCK10 p.Ala1135Thr Uncertain significance ★ ⚠ same type
DOCK10 p.Ala1175Thr Uncertain significance ★ ⚠ same type
DOCK10 p.Ala1177Ser Uncertain significance ★ ⚠ same type
DOCK10 p.Ala1271Glu 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/dock10-p-phe993leu (accessed [today's date]).

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