Is DCAF13 p.Pro141Ser (c.421C>T) pathogenic?

DCAF13 p.Pro141Ser (c.421C>T) is classified Uncertain significance in DCAF13 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-12). AlphaMissense: likely benign (0.1062); Ultra-rare (popmax 0.0267%, amr).

How common is DCAF13 p.Pro141Ser (c.421C>T) in the general population?

DCAF13 p.Pro141Ser (c.421C>T) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

What do computational predictors say about DCAF13 p.Pro141Ser (c.421C>T)?

AlphaMissense predicts likely benign (score 0.1062) — an in-silico prediction, not a clinical call.

DCAF13 p.Pro141Ser

c.421C>T · rs764577285 · VCV2403808

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1062 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1062	likely benign
REVEL	0.199	benign-leaning
SaProt	LLR -10.75	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.23	acceptor loss, 42 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 4.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 25 kb · p 0.027 · regional, not allelic
Overall
CADD	19.91	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 0.0267% Admixed American · 16/59,932 alleles

Filtering AF 0.0167% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00124% 20/1,612,424 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,746
European (non-Finnish)	0.000339%	294,808

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.Pro141Ser
Coding: c.421C>T
MANE Select: NM_015420
dbSNP: rs764577285
Type: single nucleotide variant
Location: chr8:103426098 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.84 · 3 PDB

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-pro141ser (accessed [today's date]).

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