Is CEP95 p.Arg378Trp (c.1132C>T) pathogenic?

CEP95 p.Arg378Trp (c.1132C>T) is classified Uncertain significance in CEP95 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-24). AlphaMissense: ambiguous (0.3955); Very rare (popmax 0.00483%, nfe).

How common is CEP95 p.Arg378Trp (c.1132C>T) in the general population?

CEP95 p.Arg378Trp (c.1132C>T) is very rare (popmax 0.00483%, nfe) (gnomAD).

What do computational predictors say about CEP95 p.Arg378Trp (c.1132C>T)?

AlphaMissense predicts ambiguous (score 0.3955) — an in-silico prediction, not a clinical call.

CEP95 p.Arg378Trp

c.1132C>T · VCV3266296

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3955 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00483%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3955	ambiguous
REVEL	0.286	benign-leaning
SaProt	LLR -11.14	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.33	donor loss · deltas
Pangolin	Δ0.27	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4	GERP 0.96, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 31 kb · p 0.11 · regional, not allelic
Overall
CADD	26.7	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 0.00483% European (non-Finnish) · 57/1,179,396 alleles

Filtering AF 0.00378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00345%

Overall 0.00372% 60/1,612,354 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00483%	20,691
East Asian	0.00223%	44,812
Remaining individualsnot grpmax-eligible	0.0016%	62,424
African / African-American	0.00134%	74,808

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.Arg378Trp
Coding: c.1132C>T
MANE Select: NM_138363
Type: single nucleotide variant
Location: chr17:64526180 (GRCh38)
Gene constraint: LOEUF 1.061 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.70

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

Similar variants

CEP95 p.Arg378Gln Uncertain significance ★ ⚠ same residue
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

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-arg378trp (accessed [today's date]).

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