Is CEP95 p.Ser438Pro (c.1312T>C) pathogenic?

CEP95 p.Ser438Pro (c.1312T>C) is classified Uncertain significance in CEP95 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: likely benign (0.068); Ultra-rare (popmax 0.0667%, afr).

How common is CEP95 p.Ser438Pro (c.1312T>C) in the general population?

CEP95 p.Ser438Pro (c.1312T>C) is ultra-rare (popmax 0.0667%, afr) (gnomAD).

What do computational predictors say about CEP95 p.Ser438Pro (c.1312T>C)?

AlphaMissense predicts likely benign (score 0.068) — an in-silico prediction, not a clinical call.

CEP95 p.Ser438Pro

c.1312T>C · rs377023210 · VCV2525102

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.068 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0667%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.068	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -6.61	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 -1.4	GERP -3.8
Regional constraint	o/e 1.05	unconstrained · MANE · 31 kb · p 0.11 · regional, not allelic
Overall
CADD	0.066	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

Grpmax group 0.0667% African / African-American · 50/74,962 alleles

Filtering AF 0.0519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0467%

Overall 0.00391% 63/1,611,974 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0667%	1,499
South Asian	0.00441%	22,688
East Asian	0.00223%	44,826
European (non-Finnish)	0.000678%	147,399

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: CEP95
Protein: p.Ser438Pro
Coding: c.1312T>C
MANE Select: NM_138363
dbSNP: rs377023210
Type: single nucleotide variant
Location: chr17:64529293 (GRCh38)
Gene constraint: LOEUF 1.061 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.70
Residue 438: 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-ser438pro (accessed [today's date]).

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