Is CCNH p.Lys276Met (c.827A>T) pathogenic?

CCNH p.Lys276Met (c.827A>T) is classified Uncertain significance in CCNH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-09). AlphaMissense: likely pathogenic (0.5825); Absent from gnomAD v4.1.

How common is CCNH p.Lys276Met (c.827A>T) in the general population?

CCNH p.Lys276Met (c.827A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCNH p.Lys276Met (c.827A>T)?

AlphaMissense predicts likely pathogenic (score 0.5825) — an in-silico prediction, not a clinical call.

CCNH p.Lys276Met

c.827A>T · VCV3487436

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5825 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5825	likely pathogenic
REVEL	0.368	indeterminate
SaProt	LLR -14.36	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 18 kb · p 0.18 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: CCNH
Protein: p.Lys276Met
Coding: c.827A>T
MANE Select: NM_001239
Type: single nucleotide variant
Location: chr5:87399439 (GRCh38)
Gene constraint: LOEUF 1.05 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.26 · 49 PDB
Residue 276: an α-helix

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

Similar variants

RASA1 c.1698+1G>A Pathogenic/Likely pathogenic ★★ same type
RASA1 c.2012-2A>G Pathogenic/Likely pathogenic ★★ same type
RASA1 c.2603+1G>A Pathogenic ★★ same type
RASA1 c.2691-1G>T Pathogenic/Likely pathogenic ★★ same type
RASA1 c.2925+1G>T Pathogenic ★★ same type
RASA1 c.899+1G>T Likely pathogenic ★★ same type
RASA1 p.Arg1010Ter Pathogenic ★★ same type
RASA1 p.Arg285Ter Pathogenic ★★ 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/ccnh-p-lys276met (accessed [today's date]).

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