Is DCAF12 p.Arg376Ser (c.1128G>C) pathogenic?

DCAF12 p.Arg376Ser (c.1128G>C) is classified Uncertain significance in DCAF12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-08). AlphaMissense: likely benign (0.1794); Very rare (popmax 0.00333%, amr).

How common is DCAF12 p.Arg376Ser (c.1128G>C) in the general population?

DCAF12 p.Arg376Ser (c.1128G>C) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about DCAF12 p.Arg376Ser (c.1128G>C)?

AlphaMissense predicts likely benign (score 0.1794) — an in-silico prediction, not a clinical call.

DCAF12 p.Arg376Ser

c.1128G>C · VCV3838386

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1794 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1794	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -4.23	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 0.011	GERP -1.4, phastCons 0.3
Regional constraint	o/e 0.74	unconstrained · MANE · 37 kb · p 3.4e-08 · regional, not allelic
Overall
CADD	16.98	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00333% Admixed American · 2/59,984 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,614,056 alleles · very 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: DCAF12
Protein: p.Arg376Ser
Coding: c.1128G>C
MANE Select: NM_015397
Type: single nucleotide variant
Location: chr9:34089487 (GRCh38)
Gene constraint: LOEUF 0.698 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.40 · 5 PDB

Full DCAF12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCAF12 p.Ala18Gly Uncertain significance ★ ⚠ same type
DCAF12 p.Ala222Gly Uncertain significance ★ ⚠ same type
DCAF12 p.Ala233Glu Uncertain significance ★ ⚠ same type
DCAF12 p.Ala239Thr Uncertain significance ★ ⚠ same type
DCAF12 p.Ala449Val Uncertain significance ★ ⚠ same type
DCAF12 p.Arg228Trp Uncertain significance ★ ⚠ same type
DCAF12 p.Arg297His Uncertain significance ★ ⚠ same type
DCAF12 p.Arg368Gly 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/dcaf12-p-arg376ser (accessed [today's date]).

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