Is CEP95 p.Phe129Leu (c.385T>C) pathogenic?

CEP95 p.Phe129Leu (c.385T>C) is classified Uncertain significance in CEP95 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-30). AlphaMissense: ambiguous (0.3457); Absent from gnomAD v4.1.

How common is CEP95 p.Phe129Leu (c.385T>C) in the general population?

CEP95 p.Phe129Leu (c.385T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP95 p.Phe129Leu (c.385T>C)?

AlphaMissense predicts ambiguous (score 0.3457) — an in-silico prediction, not a clinical call.

CEP95 p.Phe129Leu

c.385T>C · VCV4001215

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3457 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3457	ambiguous
REVEL	0.105	moderately benign-leaning
SaProt	LLR -4.80	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 1.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 31 kb · p 0.11 · regional, not allelic
Overall
CADD	13.73	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CEP95
Protein: p.Phe129Leu
Coding: c.385T>C
MANE Select: NM_138363
Type: single nucleotide variant
Location: chr17:64516740 (GRCh38)
Gene constraint: LOEUF 1.061 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.70
Residue 129: the 'disordered' region

Full CEP95 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP95 p.Ala188Val Uncertain significance ★ ⚠ same type
CEP95 p.Ala2Thr Uncertain significance ★ ⚠ same type
CEP95 p.Ala592Glu Uncertain significance ★ ⚠ same type
CEP95 p.Ala601Ser Uncertain significance ★ ⚠ same type
CEP95 p.Ala601Thr Uncertain significance ★ ⚠ same type
CEP95 p.Ala679Val Uncertain significance ★ ⚠ same type
CEP95 p.Arg134Gln Uncertain significance ★ ⚠ same type
CEP95 p.Arg183Gly 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/cep95-p-phe129leu (accessed [today's date]).

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