Is DCAF15 p.Ala2Val (c.5C>T) pathogenic?

DCAF15 p.Ala2Val (c.5C>T) is classified Uncertain significance in DCAF15 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-16). AlphaMissense: likely pathogenic (0.9787); Rare (popmax 0.151%, afr).

How common is DCAF15 p.Ala2Val (c.5C>T) in the general population?

DCAF15 p.Ala2Val (c.5C>T) is rare (popmax 0.151%, afr) (gnomAD).

What do computational predictors say about DCAF15 p.Ala2Val (c.5C>T)?

AlphaMissense predicts likely pathogenic (score 0.9787) — an in-silico prediction, not a clinical call.

DCAF15 p.Ala2Val

c.5C>T · VCV3499870

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9787 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.151%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9787	likely pathogenic
REVEL	0.168	moderately benign-leaning
SaProt	LLR -8.06	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.7, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 6,592 bp · p 1.2e-09 · regional, not allelic
Overall
CADD	29.4	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

Grpmax group 0.151% African / African-American · 97/64,268 alleles

Filtering AF 0.127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.118%

Overall 0.008% 100/1,249,976 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.151%	663
Remaining individualsnot grpmax-eligible	0.00434%	23,023
East Asian	0.00316%	31,610

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: DCAF15
Protein: p.Ala2Val
Coding: c.5C>T
MANE Select: NM_138353
Type: single nucleotide variant
Location: chr19:13952517 (GRCh38)
Gene constraint: LOEUF 0.502 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 78.92 · 9 PDB
Residue 2: the 'disordered' region

Full DCAF15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCAF15 p.Ile153= Benign ★★ same type
DCAF15 p.Ala149Thr Uncertain significance ★ ⚠ same type
DCAF15 p.Ala149Val Uncertain significance ★ ⚠ same type
DCAF15 p.Ala162Gly Uncertain significance ★ ⚠ same type
DCAF15 p.Ala23Gly Uncertain significance ★ ⚠ same type
DCAF15 p.Ala303Val Uncertain significance ★ ⚠ same type
DCAF15 p.Ala305Gly Uncertain significance ★ ⚠ same type
DCAF15 p.Ala316Thr 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/dcaf15-p-ala2val (accessed [today's date]).

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