Is DCAF13 p.Pro65Ser (c.193C>T) pathogenic?

DCAF13 p.Pro65Ser (c.193C>T) is classified Uncertain significance in DCAF13 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). Ultra-rare (popmax 0.0601%, eas).

How common is DCAF13 p.Pro65Ser (c.193C>T) in the general population?

DCAF13 p.Pro65Ser (c.193C>T) is ultra-rare (popmax 0.0601%, eas) (gnomAD).

DCAF13 p.Pro65Ser

c.193C>T · rs549578358 · VCV2322321

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0601%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.145	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.22	GERP -0.64
Overall
CADD	9.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0601% East Asian · 27/44,888 alleles

Filtering AF 0.0424% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0365%

Overall 0.00446% 72/1,613,370 alleles · ultra-rare exomes 61/1,460,978 · genomes 11/152,392 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0601%	1,663
South Asian	0.0406%	2,461
Remaining individualsnot grpmax-eligible	0.0112%	8,930
European (non-Finnish)	8.48e-05%	1,179,940

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.Pro65Ser
Coding: c.193C>T
MANE Select: NM_015420
dbSNP: rs549578358
Type: single nucleotide variant
Location: chr8:103415183 (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-pro65ser (accessed [today's date]).

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