Is DCAF6 p.Pro104Ser (c.310C>T) pathogenic?

DCAF6 p.Pro104Ser (c.310C>T) is classified Uncertain significance in DCAF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-29). AlphaMissense: likely pathogenic (0.9558); Ultra-rare (popmax 0.0135%, eas).

How common is DCAF6 p.Pro104Ser (c.310C>T) in the general population?

DCAF6 p.Pro104Ser (c.310C>T) is ultra-rare (popmax 0.0135%, eas) (gnomAD).

What do computational predictors say about DCAF6 p.Pro104Ser (c.310C>T)?

AlphaMissense predicts likely pathogenic (score 0.9558) — an in-silico prediction, not a clinical call.

DCAF6 p.Pro104Ser

c.310C>T · rs767000590 · VCV2531013

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9558 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9558	likely pathogenic
REVEL	0.918	moderately pathogenic-leaning
SaProt	LLR -10.67	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 66 kb · p 0.00022 · regional, not allelic
Overall
CADD	26.9	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 0.0135% East Asian · 6/44,504 alleles

Filtering AF 0.00583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00397%

Overall 0.000374% 6/1,604,314 alleles · ultra-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: DCAF6
Protein: p.Pro104Ser
Coding: c.310C>T
MANE Select: NM_001198956
dbSNP: rs767000590
Type: single nucleotide variant
Location: chr1:167974887 (GRCh38)
Gene constraint: LOEUF 0.567 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 64.23 · 1 PDB

Full DCAF6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCAF6 p.Thr644Ile Benign ★★ same type
ADCY10 c.292+6G>A Uncertain significance ★ same type
ADCY10 p.Gln283His Uncertain significance ★ ⚠ same type
ADCY10 p.Glu7Val Uncertain significance ★ ⚠ same type
ADCY10 p.Met237Thr Uncertain significance ★ ⚠ same type
ADCY10 p.Thr235Ser Uncertain significance ★ ⚠ same type
ADCY10 p.Thr254Met Conflicting classifications of pathogenicity ★ ⚠ same type
DCAF6 p.Ala295Val 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/dcaf6-p-pro104ser (accessed [today's date]).

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