Is CEP350 p.Pro91Ala (c.271C>G) pathogenic?

CEP350 p.Pro91Ala (c.271C>G) is classified Uncertain significance in CEP350 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.0651); Ultra-rare (popmax 0.0193%, eas).

How common is CEP350 p.Pro91Ala (c.271C>G) in the general population?

CEP350 p.Pro91Ala (c.271C>G) is ultra-rare (popmax 0.0193%, eas) (gnomAD).

What do computational predictors say about CEP350 p.Pro91Ala (c.271C>G)?

AlphaMissense predicts likely benign (score 0.0651) — an in-silico prediction, not a clinical call.

CEP350 p.Pro91Ala

c.271C>G · rs762781537 · VCV3142871

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0651 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0193%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0651	likely benign
REVEL	0.023	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.08	GERP 2.4, phastCons 0.85
Regional constraint	o/e 0.97	unconstrained · MANE · 67 kb · p 0.23 · regional, not allelic
Overall
CADD	18.6	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 0.0193% East Asian · 8/41,488 alleles

Filtering AF 0.00956% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00696%

Overall 0.000579% 9/1,554,568 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0193%	5,186
Remaining individualsnot grpmax-eligible	0.00166%	60,066

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: CEP350
Protein: p.Pro91Ala
Coding: c.271C>G
MANE Select: NM_014810
dbSNP: rs762781537
Type: single nucleotide variant
Location: chr1:179992097 (GRCh38)
Gene constraint: LOEUF 0.402 · pLI 1.00 (gnomAD)

Full CEP350 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP350 p.Asp522Gly Benign ★★ same type
CEP350 p.His1462Arg Likely benign ★★ same type
CEP350 p.Ile1905Met Likely benign ★★ same type
CEP350 p.Lys2735Asn Benign ★★ same type
CEP350 c.5567+1G>A Uncertain significance ★ same type
CEP350 p.Ala1096Thr Uncertain significance ★ ⚠ same type
CEP350 p.Ala1160Thr Uncertain significance ★ ⚠ same type
CEP350 p.Ala1163Pro 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/cep350-p-pro91ala (accessed [today's date]).

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