Is CCDC92 p.Ala226Val (c.677C>T) pathogenic?

CCDC92 p.Ala226Val (c.677C>T) is classified Uncertain significance in CCDC92 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-03). AlphaMissense: likely benign (0.1055); Absent from gnomAD v4.1.

How common is CCDC92 p.Ala226Val (c.677C>T) in the general population?

CCDC92 p.Ala226Val (c.677C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC92 p.Ala226Val (c.677C>T)?

AlphaMissense predicts likely benign (score 0.1055) — an in-silico prediction, not a clinical call.

CCDC92 p.Ala226Val

c.677C>T · rs1311068677 · VCV2315921

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1055 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1055	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -6.67	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 5.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 7,244 bp · p 0.054 · regional, not allelic
Overall
CADD	19.76	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

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: CCDC92
Protein: p.Ala226Val
Coding: c.677C>T
MANE Select: NM_025140
dbSNP: rs1311068677
Type: single nucleotide variant
Location: chr12:123937377 (GRCh38)
Gene constraint: LOEUF 0.738 · pLI 0.25 (gnomAD)
Structure: AlphaFold pLDDT 73.80

Full CCDC92 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC92 p.Ala114Thr Uncertain significance ★ ⚠ same type
CCDC92 p.Ala178Asp Uncertain significance ★ ⚠ same type
CCDC92 p.Ala269Thr Uncertain significance ★ ⚠ same type
CCDC92 p.Ala93Val Uncertain significance ★ ⚠ same type
CCDC92 p.Arg203His Uncertain significance ★ ⚠ same type
CCDC92 p.Arg223Gly Uncertain significance ★ ⚠ same type
CCDC92 p.Arg234Gln Uncertain significance ★ ⚠ same type
CCDC92 p.Arg250Thr 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/ccdc92-p-ala226val (accessed [today's date]).

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