Is DCAF13 p.Val3Ala (c.8T>C) pathogenic?

DCAF13 p.Val3Ala (c.8T>C) is classified Uncertain significance in DCAF13 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-20). AlphaMissense: likely pathogenic (0.8524); Ultra-rare (popmax 0.0734%, amr).

How common is DCAF13 p.Val3Ala (c.8T>C) in the general population?

DCAF13 p.Val3Ala (c.8T>C) is ultra-rare (popmax 0.0734%, amr) (gnomAD).

What do computational predictors say about DCAF13 p.Val3Ala (c.8T>C)?

AlphaMissense predicts likely pathogenic (score 0.8524) — an in-silico prediction, not a clinical call.

DCAF13 p.Val3Ala

c.8T>C · VCV3499856

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8524 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0734%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8524	likely pathogenic
REVEL	0.841	moderately pathogenic-leaning
SaProt	LLR -11.66	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 25 kb · p 0.027 · regional, not allelic
Overall
CADD	28.7	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

Grpmax group 0.0734% Admixed American · 44/59,946 alleles

Filtering AF 0.0561% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0501%

Overall 0.00273% 44/1,613,166 alleles · ultra-rare

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: DCAF13
Protein: p.Val3Ala
Coding: c.8T>C
MANE Select: NM_015420
Type: single nucleotide variant
Location: chr8:103415454 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.84 · 3 PDB
Residue 3: a β-strand

Full DCAF13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCAF13 p.His327Arg Uncertain significance ★★ ⚠ same type
DCAF13 p.Phe381Cys Uncertain significance ★★ ⚠ same type
DCAF13 p.Ala109Gly Benign ★★ same type
DCAF13 p.Ala70= Benign ★★ same type
DCAF13 c.-20C>T Uncertain significance ★ same type
DCAF13 c.-30T>C Uncertain significance ★ same type
DCAF13 c.-33A>G Uncertain significance ★ same type
DCAF13 c.-38C>A 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/dcaf13-p-val3ala (accessed [today's date]).

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