Is DCAF5 p.Pro176Ser (c.526C>T) pathogenic?

DCAF5 p.Pro176Ser (c.526C>T) is classified Uncertain significance in DCAF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.0818); Ultra-rare (popmax 0.0132%, sas).

How common is DCAF5 p.Pro176Ser (c.526C>T) in the general population?

DCAF5 p.Pro176Ser (c.526C>T) is ultra-rare (popmax 0.0132%, sas) (gnomAD).

What do computational predictors say about DCAF5 p.Pro176Ser (c.526C>T)?

AlphaMissense predicts likely benign (score 0.0818) — an in-silico prediction, not a clinical call.

DCAF5 p.Pro176Ser

c.526C>T · rs747834181 · VCV3080319

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0818 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0818	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -6.82	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 61 kb · p 6.5e-22 · regional, not allelic
Overall
CADD	22.3	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 0.0132% South Asian · 12/91,074 alleles

Filtering AF 0.00751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.000806% 13/1,613,768 alleles · ultra-rare exomes 11/1,461,606 · genomes 2/152,162 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0132%	7,589
African / African-American	0.00134%	74,878

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: DCAF5
Protein: p.Pro176Ser
Coding: c.526C>T
MANE Select: NM_003861
dbSNP: rs747834181
Type: single nucleotide variant
Location: chr14:69118148 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.00 · 2 PDB

Full DCAF5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCAF5 p.Ala189Pro Uncertain significance ★ ⚠ same type
DCAF5 p.Ala250Asp Uncertain significance ★ ⚠ same type
DCAF5 p.Ala405Thr Uncertain significance ★ ⚠ same type
DCAF5 p.Ala526Thr Uncertain significance ★ ⚠ same type
DCAF5 p.Ala647Pro Uncertain significance ★ ⚠ same type
DCAF5 p.Ala800Pro Uncertain significance ★ ⚠ same type
DCAF5 p.Arg291Cys Uncertain significance ★ ⚠ same type
DCAF5 p.Arg375Gln 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/dcaf5-p-pro176ser (accessed [today's date]).

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