Is CCNH p.Met54Val (c.160A>G) pathogenic?

CCNH p.Met54Val (c.160A>G) is classified Benign in CCNH (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-29). AlphaMissense: likely benign (0.0754); Low-frequency (popmax 4.09%, afr).

How common is CCNH p.Met54Val (c.160A>G) in the general population?

CCNH p.Met54Val (c.160A>G) is low-frequency (popmax 4.09%, afr) (gnomAD).

What do computational predictors say about CCNH p.Met54Val (c.160A>G)?

AlphaMissense predicts likely benign (score 0.0754) — an in-silico prediction, not a clinical call.

CCNH p.Met54Val

c.160A>G · rs3093785 · VCV788984

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0754 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.09%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0754	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -4.39	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 0.68	GERP -0.92, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 18 kb · p 0.18 · regional, not allelic
Overall
CADD	13.19	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 4.09% African / African-American · 3,066/74,944 alleles

Filtering AF 3.97% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.92%

Overall 0.229% 3,692/1,612,510 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.09%	24
Middle Eastern	0.396%	252
Remaining individualsnot grpmax-eligible	0.346%	289
Admixed American	0.311%	321
European (non-Finnish)	0.0161%	6,207
South Asian	0.00992%	10,078
East Asian	0.00223%	44,790

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.Met54Val
Coding: c.160A>G
MANE Select: NM_001239
dbSNP: rs3093785
Type: single nucleotide variant
Location: chr5:87411304 (GRCh38)
Gene constraint: LOEUF 1.05 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.26 · 49 PDB
Residue 54: a UniProt-annotated variant site (in); 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-met54val (accessed [today's date]).

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