Is DCAF15 p.Pro339Ser (c.1015C>T) pathogenic?

DCAF15 p.Pro339Ser (c.1015C>T) is classified Likely benign in DCAF15 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-24). AlphaMissense: likely benign (0.0637); Ultra-rare (popmax 0.0133%, amr).

How common is DCAF15 p.Pro339Ser (c.1015C>T) in the general population?

DCAF15 p.Pro339Ser (c.1015C>T) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about DCAF15 p.Pro339Ser (c.1015C>T)?

AlphaMissense predicts likely benign (score 0.0637) — an in-silico prediction, not a clinical call.

DCAF15 p.Pro339Ser

c.1015C>T · rs750637838 · VCV2529496

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0637 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0637	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -6.46	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 -0.25	GERP -3.4
Regional constraint	o/e 1.05	unconstrained · MANE · 674 bp · p 0.47 · regional, not allelic
Overall
CADD	0.944	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 0.0133% Admixed American · 8/60,010 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.000548% 8/1,458,972 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: DCAF15
Protein: p.Pro339Ser
Coding: c.1015C>T
MANE Select: NM_138353
dbSNP: rs750637838
Type: single nucleotide variant
Location: chr19:13959275 (GRCh38)
Gene constraint: LOEUF 0.502 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 78.92 · 9 PDB

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.Ala2Val Uncertain significance ★ ⚠ same type
DCAF15 p.Ala303Val Uncertain significance ★ ⚠ same type
DCAF15 p.Ala305Gly 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-pro339ser (accessed [today's date]).

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