Is CENPM p.Phe92Cys (c.275T>G) pathogenic?

CENPM p.Phe92Cys (c.275T>G) is classified Uncertain significance in CENPM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: ambiguous (0.4324); Very rare (popmax 0.0022%, sas).

How common is CENPM p.Phe92Cys (c.275T>G) in the general population?

CENPM p.Phe92Cys (c.275T>G) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about CENPM p.Phe92Cys (c.275T>G)?

AlphaMissense predicts ambiguous (score 0.4324) — an in-silico prediction, not a clinical call.

CENPM p.Phe92Cys

c.275T>G · VCV4225715

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4324 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Computational evidence

Protein change
AlphaMissense	0.4324	ambiguous
REVEL	0.383	indeterminate
SaProt	LLR -10.69	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 0.56, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 8,017 bp · p 0.48 · regional, not allelic
Overall
CADD	23.4	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 0.0022% South Asian · 2/91,074 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000616% 9/1,461,860 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,537
African / African-American	0.00133%	74,948
European (non-Finnish)	0.000508%	196,669

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: CENPM
Protein: p.Phe92Cys
Coding: c.275T>G
MANE Select: NM_024053
Type: single nucleotide variant
Location: chr22:41945260 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.38 · 14 PDB
Residue 92: an α-helix

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

Similar variants

CENPM p.Ala16Asp Uncertain significance ★ ⚠ same type
CENPM p.Arg106Trp Uncertain significance ★ ⚠ same type
CENPM p.Arg114Trp Uncertain significance ★ ⚠ same type
CENPM p.Arg145His Uncertain significance ★ ⚠ same type
CENPM p.Arg148His Uncertain significance ★ ⚠ same type
CENPM p.Arg86Pro Uncertain significance ★ ⚠ same type
CENPM p.Asn14Ser Uncertain significance ★ ⚠ same type
CENPM p.Cys131Ser 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/cenpm-p-phe92cys (accessed [today's date]).

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