Is CENPH p.Ile140Val (c.418A>G) pathogenic?

CENPH p.Ile140Val (c.418A>G) is classified Uncertain significance in CENPH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-16). AlphaMissense: likely benign (0.0903); Absent from gnomAD v4.1.

How common is CENPH p.Ile140Val (c.418A>G) in the general population?

CENPH p.Ile140Val (c.418A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CENPH p.Ile140Val (c.418A>G)?

AlphaMissense predicts likely benign (score 0.0903) — an in-silico prediction, not a clinical call.

CENPH p.Ile140Val

c.418A>G · VCV3490360

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0903 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,566,542)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0903	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -6.58	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 3.8	GERP -1.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 20 kb · p 0.6 · regional, not allelic
Overall
CADD	11.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

No allele count reported in gnomAD v4.1 (AN 1,566,542). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CENPH
Protein: p.Ile140Val
Coding: c.418A>G
MANE Select: NM_022909
Type: single nucleotide variant
Location: chr5:69202552 (GRCh38)
Gene constraint: LOEUF 1.944 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 13 PDB
Residue 140: 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-ile140val (accessed [today's date]).

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