Is DCAF7 p.Pro16Ser (c.46C>T) pathogenic?

DCAF7 p.Pro16Ser (c.46C>T) is classified Uncertain significance in DCAF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-07). AlphaMissense: likely pathogenic (0.5816); Ultra-rare (popmax 0.0133%, amr).

How common is DCAF7 p.Pro16Ser (c.46C>T) in the general population?

DCAF7 p.Pro16Ser (c.46C>T) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about DCAF7 p.Pro16Ser (c.46C>T)?

AlphaMissense predicts likely pathogenic (score 0.5816) — an in-silico prediction, not a clinical call.

DCAF7 p.Pro16Ser

c.46C>T · rs772876029 · VCV3080333

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5816 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5816	likely pathogenic
REVEL	0.258	benign-leaning
SaProt	LLR -12.86	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.30	constrained · MANE · 38 kb · p 9.5e-50 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/60,010 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.00161% 26/1,613,790 alleles · ultra-rare exomes 23/1,461,536 · genomes 3/152,254 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,501
African / African-American	0.00267%	37,471
European (non-Finnish)	0.00136%	73,740

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: DCAF7
Protein: p.Pro16Ser
Coding: c.46C>T
MANE Select: NM_005828
dbSNP: rs772876029
Type: single nucleotide variant
Location: chr17:63550723 (GRCh38)
Gene constraint: LOEUF 0.235 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.35

Full DCAF7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCAF7 p.Gln169= Benign ★★ same type
DCAF7 p.Gly82= Benign ★★ same type
DCAF7 p.Asp53Gly Uncertain significance ★ ⚠ same type
DCAF7 p.Glu58Gly Uncertain significance ★ same type
DCAF7 p.Gly186Trp Uncertain significance ★ ⚠ same type
DCAF7 p.Met299Val Uncertain significance ★ ⚠ same type
DCAF7 p.Phe65Val Uncertain significance ★ ⚠ same type
DCAF7 p.Val201Met 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/dcaf7-p-pro16ser (accessed [today's date]).

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