Is CCDC27 p.Val359Ala (c.1076T>C) pathogenic?

CCDC27 p.Val359Ala (c.1076T>C) is classified Likely benign in CCDC27 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-14). AlphaMissense: likely benign (0.1258); Absent from gnomAD v4.1.

How common is CCDC27 p.Val359Ala (c.1076T>C) in the general population?

CCDC27 p.Val359Ala (c.1076T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC27 p.Val359Ala (c.1076T>C)?

AlphaMissense predicts likely benign (score 0.1258) — an in-silico prediction, not a clinical call.

CCDC27 p.Val359Ala

c.1076T>C · VCV3486621

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1258 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1258	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -5.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.096	GERP -3
Regional constraint	o/e 1.01	unconstrained · MANE · 19 kb · p 0.84 · regional, not allelic
Overall
CADD	0.014	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCDC27
Protein: p.Val359Ala
Coding: c.1076T>C
MANE Select: NM_152492
Type: single nucleotide variant
Location: chr1:3763229 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.70
Residue 359: the 'disordered' region

Full CCDC27 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC27 p.Ala112Pro Uncertain significance ★ ⚠ same type
CCDC27 p.Ala112Val Uncertain significance ★ ⚠ same type
CCDC27 p.Ala153Val Uncertain significance ★ ⚠ same type
CCDC27 p.Ala293Thr Uncertain significance ★ ⚠ same type
CCDC27 p.Ala324Val Uncertain significance ★ ⚠ same type
CCDC27 p.Ala574Val Uncertain significance ★ ⚠ same type
CCDC27 p.Ala78Asp Uncertain significance ★ ⚠ same type
CCDC27 p.Ala78Thr 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/ccdc27-p-val359ala (accessed [today's date]).

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