Is CCNH p.Leu238Pro (c.713T>C) pathogenic?

CCNH p.Leu238Pro (c.713T>C) is classified Uncertain significance in CCNH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). AlphaMissense: likely benign (0.3115); Very rare (popmax 8.55e-05%, nfe).

How common is CCNH p.Leu238Pro (c.713T>C) in the general population?

CCNH p.Leu238Pro (c.713T>C) is very rare (popmax 8.55e-05%, nfe) (gnomAD).

What do computational predictors say about CCNH p.Leu238Pro (c.713T>C)?

AlphaMissense predicts likely benign (score 0.3115) — an in-silico prediction, not a clinical call.

CCNH p.Leu238Pro

c.713T>C · rs2530700434 · VCV2524152

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3115 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.55e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3115	likely benign
REVEL	0.41	indeterminate
SaProt	LLR -12.96	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 18 kb · p 0.18 · regional, not allelic
Overall
CADD	26.3	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

Grpmax group 8.55e-05% European (non-Finnish) · 1/1,170,184 alleles

Overall 6.96e-05% 1/1,436,938 alleles · very rare

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: CCNH
Protein: p.Leu238Pro
Coding: c.713T>C
MANE Select: NM_001239
dbSNP: rs2530700434
Type: single nucleotide variant
Location: chr5:87401749 (GRCh38)
Gene constraint: LOEUF 1.05 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.26 · 49 PDB
Residue 238: a turn

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-leu238pro (accessed [today's date]).

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