Is CCDC71 p.Arg250Gln (c.749G>A) pathogenic?

CCDC71 p.Arg250Gln (c.749G>A) is classified Likely benign in CCDC71 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-23). AlphaMissense: likely benign (0.0687); Ultra-rare (popmax 0.0185%, nfe).

How common is CCDC71 p.Arg250Gln (c.749G>A) in the general population?

CCDC71 p.Arg250Gln (c.749G>A) is ultra-rare (popmax 0.0185%, nfe) (gnomAD).

What do computational predictors say about CCDC71 p.Arg250Gln (c.749G>A)?

AlphaMissense predicts likely benign (score 0.0687) — an in-silico prediction, not a clinical call.

CCDC71 p.Arg250Gln

c.749G>A · rs145288601 · VCV2472895

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0687 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0185%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0687	likely benign
REVEL	0.004	strongly benign-leaning
SaProt	LLR -7.13	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 -1.3	GERP -3.6, phastCons 0.001
Regional constraint	o/e 1.08	unconstrained · MANE · 1,135 bp · p 0.091 · regional, not allelic
Overall
CADD	4.727	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 0.0185% European (non-Finnish) · 218/1,180,048 alleles

Filtering AF 0.0165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0157%

Overall 0.0147% 237/1,614,234 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0185%	5,413
Remaining individualsnot grpmax-eligible	0.016%	6,251
East Asian	0.00669%	14,958
African / African-American	0.00533%	18,766
Finnishnot grpmax-eligible	0.00312%	32,017

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.Arg250Gln
Coding: c.749G>A
MANE Select: NM_022903
dbSNP: rs145288601
Type: single nucleotide variant
Location: chr3:49163460 (GRCh38)
Gene constraint: LOEUF 1.135 · pLI 0.26 (gnomAD)
Structure: AlphaFold pLDDT 52.59
Residue 250: 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-arg250gln (accessed [today's date]).

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