Is DCAF4 p.Arg344Pro (c.1031G>C) pathogenic?

DCAF4 p.Arg344Pro (c.1031G>C) is classified Uncertain significance in DCAF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-08). AlphaMissense: likely pathogenic (0.9776); Very rare (popmax 0.00017%, nfe).

How common is DCAF4 p.Arg344Pro (c.1031G>C) in the general population?

DCAF4 p.Arg344Pro (c.1031G>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about DCAF4 p.Arg344Pro (c.1031G>C)?

AlphaMissense predicts likely pathogenic (score 0.9776) — an in-silico prediction, not a clinical call.

DCAF4 p.Arg344Pro

c.1031G>C · VCV4658624

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9776 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9776	likely pathogenic · top 4% in DCAF4
REVEL	0.655	pathogenic-leaning
SaProt	LLR -16.93	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.6	GERP 0.71, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 21 kb · p 0.0042 · 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 0.00017% European (non-Finnish) · 2/1,179,942 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,996 alleles · very rare exomes 2/1,461,722 · genomes 0/152,274 · joint denominator

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: DCAF4
Protein: p.Arg344Pro
Coding: c.1031G>C
MANE Select: NM_015604
Type: single nucleotide variant
Location: chr14:72955548 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.34 · 1 PDB

Full DCAF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCAF4 p.Ser28= Benign ★★ same type
DCAF4 p.Ser325Gly Likely benign ★★ same type
DCAF4 p.Ala125Val Uncertain significance ★ ⚠ same type
DCAF4 p.Ala168Gly Uncertain significance ★ ⚠ same type
DCAF4 p.Ala179Thr Uncertain significance ★ ⚠ same type
DCAF4 p.Ala233Val Uncertain significance ★ ⚠ same type
DCAF4 p.Ala285Ser Uncertain significance ★ ⚠ same type
DCAF4 p.Ala461Thr 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/dcaf4-p-arg344pro (accessed [today's date]).

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