Is CENPH p.Val94Ile (c.280G>A) pathogenic?

CENPH p.Val94Ile (c.280G>A) is classified Likely benign in CENPH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely benign (0.0682); Very rare (popmax 0.00414%, afr).

How common is CENPH p.Val94Ile (c.280G>A) in the general population?

CENPH p.Val94Ile (c.280G>A) is very rare (popmax 0.00414%, afr) (gnomAD).

What do computational predictors say about CENPH p.Val94Ile (c.280G>A)?

AlphaMissense predicts likely benign (score 0.0682) — an in-silico prediction, not a clinical call.

CENPH p.Val94Ile

c.280G>A · VCV4225684

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0682 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00414%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0682	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -5.93	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 0.07	GERP -5.6
Regional constraint	o/e 1.03	unconstrained · MANE · 20 kb · p 0.6 · regional, not allelic
Overall
CADD	0.12	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 0.00414% African / African-American · 3/72,508 alleles

Filtering AF 0.0011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000505%

Overall 0.000192% 3/1,563,990 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: CENPH
Protein: p.Val94Ile
Coding: c.280G>A
MANE Select: NM_022909
Type: single nucleotide variant
Location: chr5:69195757 (GRCh38)
Gene constraint: LOEUF 1.944 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 13 PDB
Residue 94: an α-helix

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

Similar variants

CENPH p.Ala22Gly Uncertain significance ★ ⚠ same type
CENPH p.Ala33Val Uncertain significance ★ ⚠ same type
CENPH p.Ala48Thr Uncertain significance ★ ⚠ same type
CENPH p.Arg21Trp Uncertain significance ★ ⚠ same type
CENPH p.Arg39His Uncertain significance ★ ⚠ same type
CENPH p.Arg47Thr Uncertain significance ★ ⚠ same type
CENPH p.Asp128Gly Uncertain significance ★ ⚠ same type
CENPH p.Asp38Glu 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/cenph-p-val94ile (accessed [today's date]).

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