Is CCDC34 p.Arg27Trp (c.79C>T) pathogenic?

CCDC34 p.Arg27Trp (c.79C>T) is classified Uncertain significance in CCDC34 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-04). AlphaMissense: likely benign (0.158); Very rare (popmax 0.00524%, nfe).

How common is CCDC34 p.Arg27Trp (c.79C>T) in the general population?

CCDC34 p.Arg27Trp (c.79C>T) is very rare (popmax 0.00524%, nfe) (gnomAD).

What do computational predictors say about CCDC34 p.Arg27Trp (c.79C>T)?

AlphaMissense predicts likely benign (score 0.158) — an in-silico prediction, not a clinical call.

CCDC34 p.Arg27Trp

c.79C>T · VCV3486676

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.158 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00524%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.158	likely benign
REVEL	0.149	moderately benign-leaning
SaProt	LLR -7.72	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 6	GERP 2.2, phastCons 0.99
Regional constraint	o/e 1.03	unconstrained · MANE · 24 kb · p 0.52 · regional, not allelic
Overall
CADD	24.8	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 0.00524% European (non-Finnish) · 61/1,164,392 alleles

Filtering AF 0.00416% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00377%

Overall 0.00392% 62/1,583,088 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00524%	19,088
Finnishnot grpmax-eligible	0.00165%	60,560

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: CCDC34
Protein: p.Arg27Trp
Coding: c.79C>T
MANE Select: NM_030771
Type: single nucleotide variant
Location: chr11:27363116 (GRCh38)
Gene constraint: LOEUF 1.08 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.46
Residue 27: the 'disordered' region

Full CCDC34 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC34 p.Ala100Val Uncertain significance ★ ⚠ same type
CCDC34 p.Ala20Thr Uncertain significance ★ ⚠ same type
CCDC34 p.Ala297Asp Uncertain significance ★ ⚠ same type
CCDC34 p.Arg136His Uncertain significance ★ ⚠ same type
CCDC34 p.Arg141His Uncertain significance ★ ⚠ same type
CCDC34 p.Arg141Leu Uncertain significance ★ ⚠ same type
CCDC34 p.Arg159Gln Uncertain significance ★ ⚠ same type
CCDC34 p.Arg41Leu 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/ccdc34-p-arg27trp (accessed [today's date]).

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