Is CEP295 p.Arg1373Gln (c.4118G>A) pathogenic?

CEP295 p.Arg1373Gln (c.4118G>A) is classified Likely benign in CEP295 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-05). AlphaMissense: likely benign (0.0649); Ultra-rare (popmax 0.0166%, mid).

How common is CEP295 p.Arg1373Gln (c.4118G>A) in the general population?

CEP295 p.Arg1373Gln (c.4118G>A) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about CEP295 p.Arg1373Gln (c.4118G>A)?

AlphaMissense predicts likely benign (score 0.0649) — an in-silico prediction, not a clinical call.

CEP295 p.Arg1373Gln

c.4118G>A · rs768415947 · VCV2332989

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0649 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0649	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -2.15	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 0.15	GERP -3
Regional constraint	o/e 0.98	unconstrained · MANE · 35 kb · p 0.4 · regional, not allelic
Overall
CADD	8.284	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 0.0166% Middle Eastern · 1/6,018 alleles

Filtering AF 0.00205% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00181%

Overall 0.00272% 42/1,546,404 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,018
African / African-American	0.00411%	24,342
South Asian	0.00357%	28,019
European (non-Finnish)	0.00288%	34,759
East Asian	0.00244%	40,922
Remaining individualsnot grpmax-eligible	0.00166%	60,154

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.Arg1373Gln
Coding: c.4118G>A
MANE Select: NM_033395
dbSNP: rs768415947
Type: single nucleotide variant
Location: chr11:93699030 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 44.76
Residue 1373: a UniProt-annotated variant site (in sckl11; likely pathogenic)

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

Similar variants

CEP295 p.Arg1373Trp 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-arg1373gln (accessed [today's date]).

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