Is CEP295 p.Ile48Met (c.144A>G) pathogenic?

CEP295 p.Ile48Met (c.144A>G) is classified Uncertain significance in CEP295 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). AlphaMissense: likely benign (0.3128); Very rare (popmax 0.00201%, nfe).

How common is CEP295 p.Ile48Met (c.144A>G) in the general population?

CEP295 p.Ile48Met (c.144A>G) is very rare (popmax 0.00201%, nfe) (gnomAD).

What do computational predictors say about CEP295 p.Ile48Met (c.144A>G)?

AlphaMissense predicts likely benign (score 0.3128) — an in-silico prediction, not a clinical call.

CEP295 p.Ile48Met

c.144A>G · VCV3831857

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3128 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00201%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3128	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -6.76	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 3.4	GERP 0.65, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 25 kb · p 0.36 · regional, not allelic
Overall
CADD	22.0	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 0.00201% European (non-Finnish) · 23/1,146,664 alleles

Filtering AF 0.00134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00112%

Overall 0.00172% 24/1,398,932 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00201%	49,855
Remaining individualsnot grpmax-eligible	0.00166%	60,140

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.Ile48Met
Coding: c.144A>G
MANE Select: NM_033395
Type: single nucleotide variant
Location: chr11:93667642 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 44.76
Residue 48: 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.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
CEP295 p.Glu179Lys 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-ile48met (accessed [today's date]).

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