Is CEP295 p.Arg293His (c.878G>A) pathogenic?

CEP295 p.Arg293His (c.878G>A) is classified Uncertain significance in CEP295 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-28). AlphaMissense: likely benign (0.223); Rare (popmax 0.312%, afr).

How common is CEP295 p.Arg293His (c.878G>A) in the general population?

CEP295 p.Arg293His (c.878G>A) is rare (popmax 0.312%, afr) (gnomAD).

What do computational predictors say about CEP295 p.Arg293His (c.878G>A)?

AlphaMissense predicts likely benign (score 0.223) — an in-silico prediction, not a clinical call.

CEP295 p.Arg293His

c.878G>A · rs371875146 · VCV2354505

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.223 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.312%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.223	likely benign
REVEL	0.228	benign-leaning
SaProt	LLR -7.10	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 8.5	GERP 2.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 25 kb · p 0.36 · regional, not allelic
Overall
CADD	29.3	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 0.312% African / African-American · 228/73,072 alleles

Filtering AF 0.279% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.266%

Overall 0.0169% 262/1,550,200 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.312%	320
Middle Eastern	0.0334%	2,995
Admixed American	0.0158%	6,311
Remaining individualsnot grpmax-eligible	0.0117%	8,581
European (non-Finnish)	0.00148%	67,449

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: CEP295
Protein: p.Arg293His
Coding: c.878G>A
MANE Select: NM_033395
dbSNP: rs371875146
Type: single nucleotide variant
Location: chr11:93683671 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 44.76
Residue 293: the 'necessary for centriole targeting and microtubule association' region

Full CEP295 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP295 p.Arg293Cys Uncertain significance ★ ⚠ same residue
CEP295 p.Gln2146His Uncertain significance ★★ ⚠ same type
CEP295 p.Gln998Arg Uncertain significance ★★ ⚠ same type
CEP295 p.Thr451Arg Uncertain significance ★★ ⚠ same type
CEP295 p.Gln1506= Benign ★★ same type
CEP295 p.Gln1728= Benign ★★ same type
CEP295 p.Gln80Lys Benign ★★ same type
CEP295 p.Glu1026Lys Benign ★★ ⚠ 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/cep295-p-arg293his (accessed [today's date]).

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