Is CCDC71 p.Arg357Trp (c.1069C>T) pathogenic?

CCDC71 p.Arg357Trp (c.1069C>T) is classified Uncertain significance in CCDC71 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-06). AlphaMissense: likely benign (0.0912); Ultra-rare (popmax 0.0165%, mid).

How common is CCDC71 p.Arg357Trp (c.1069C>T) in the general population?

CCDC71 p.Arg357Trp (c.1069C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CCDC71 p.Arg357Trp (c.1069C>T)?

AlphaMissense predicts likely benign (score 0.0912) — an in-silico prediction, not a clinical call.

CCDC71 p.Arg357Trp

c.1069C>T · rs201052008 · VCV3139329

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0912 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0912	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -10.23	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Regional constraint	o/e 1.08	unconstrained · MANE · 1,135 bp · p 0.091 · regional, not allelic
Overall
CADD	14.03	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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.0092% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0072%

Overall 0.00173% 28/1,614,142 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
African / African-American	0.016%	6,257
East Asian	0.00446%	22,436
Remaining individualsnot grpmax-eligible	0.0016%	62,508
South Asian	0.0011%	91,092
European (non-Finnish)	0.000932%	107,274

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: CCDC71
Protein: p.Arg357Trp
Coding: c.1069C>T
MANE Select: NM_022903
dbSNP: rs201052008
Type: single nucleotide variant
Location: chr3:49163140 (GRCh38)
Gene constraint: LOEUF 1.135 · pLI 0.26 (gnomAD)
Structure: AlphaFold pLDDT 52.59
Residue 357: the 'disordered' region

Full CCDC71 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC71 p.Ala106Pro Uncertain significance ★ ⚠ same type
CCDC71 p.Ala126Thr Uncertain significance ★ ⚠ same type
CCDC71 p.Ala128Val Uncertain significance ★ ⚠ same type
CCDC71 p.Ala132Ser Uncertain significance ★ ⚠ same type
CCDC71 p.Ala181Gly Uncertain significance ★ ⚠ same type
CCDC71 p.Ala246Pro Uncertain significance ★ ⚠ same type
CCDC71 p.Ala281Gly Uncertain significance ★ ⚠ same type
CCDC71 p.Ala283Asp 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/ccdc71-p-arg357trp (accessed [today's date]).

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