Is CCDC6 p.Val239Ile (c.715G>A) pathogenic?

CCDC6 p.Val239Ile (c.715G>A) is classified Uncertain significance in CCDC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.1488); Very rare (popmax 0.00669%, afr).

How common is CCDC6 p.Val239Ile (c.715G>A) in the general population?

CCDC6 p.Val239Ile (c.715G>A) is very rare (popmax 0.00669%, afr) (gnomAD).

What do computational predictors say about CCDC6 p.Val239Ile (c.715G>A)?

AlphaMissense predicts likely benign (score 0.1488) — an in-silico prediction, not a clinical call.

CCDC6 p.Val239Ile

c.715G>A · rs775541001 · VCV2362821

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1488 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1488	likely benign
REVEL	0.308	indeterminate
SaProt	LLR -7.15	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.6, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 8,310 bp · p 1.3e-08 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00669% African / African-American · 5/74,700 alleles

Filtering AF 0.00395% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00361%

Overall 0.00435% 70/1,607,780 alleles · very rare exomes 66/1,455,652 · genomes 4/152,128 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00669%	14,940
European (non-Finnish)	0.00501%	19,947
Remaining individualsnot grpmax-eligible	0.00321%	31,118
East Asian	0.00223%	44,744
South Asian	0.00223%	44,835
Finnishnot grpmax-eligible	0.00156%	63,932

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: CCDC6
Protein: p.Val239Ile
Coding: c.715G>A
MANE Select: NM_005436
dbSNP: rs775541001
Type: single nucleotide variant
Location: chr10:59812767 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI 0.89 (gnomAD)
Structure: AlphaFold pLDDT 76.03 · 2 PDB

Full CCDC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC6 p.Val239Ala Uncertain significance ★ ⚠ same residue
CCDC6 p.Leu206= Benign ★★ same type
CCDC6 p.Ala13Thr Uncertain significance ★ ⚠ same type
CCDC6 p.Arg197Gln Uncertain significance ★ ⚠ same type
CCDC6 p.Arg271Gln Uncertain significance ★ ⚠ same type
CCDC6 p.Arg298Thr Uncertain significance ★ ⚠ same type
CCDC6 p.Arg415Gln Uncertain significance ★ ⚠ same type
CCDC6 p.Asn267Ser 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/ccdc6-p-val239ile (accessed [today's date]).

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