Is CEP97 p.Ser331Arg (c.991A>C) pathogenic?

CEP97 p.Ser331Arg (c.991A>C) is classified Uncertain significance in CEP97 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-04). AlphaMissense: ambiguous (0.3554); Very rare (popmax 0.00447%, eas).

How common is CEP97 p.Ser331Arg (c.991A>C) in the general population?

CEP97 p.Ser331Arg (c.991A>C) is very rare (popmax 0.00447%, eas) (gnomAD).

What do computational predictors say about CEP97 p.Ser331Arg (c.991A>C)?

AlphaMissense predicts ambiguous (score 0.3554) — an in-silico prediction, not a clinical call.

CEP97 p.Ser331Arg

c.991A>C · VCV4744831

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3554 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00447%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3554	ambiguous
REVEL	0.045	moderately benign-leaning
SaProt	LLR -7.88	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.11, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 41 kb · p 0.018 · regional, not allelic
Overall
CADD	19.9	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 0.00447% East Asian · 2/44,760 alleles

Filtering AF 0.000741% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000124% 2/1,611,994 alleles · very rare

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: CEP97
Protein: p.Ser331Arg
Coding: c.991A>C
MANE Select: NM_024548
Type: single nucleotide variant
Location: chr3:101757160 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.89
Residue 331: the 'ccp110-binding' region

Full CEP97 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP97 p.Ala164Thr Uncertain significance ★★ ⚠ same type
CEP97 p.Ala624Gly Uncertain significance ★★ ⚠ same type
CEP97 p.Arg259Gln Uncertain significance ★★ ⚠ same type
CEP97 p.Arg468Ile Uncertain significance ★★ ⚠ same type
CEP97 p.Arg570Gln Uncertain significance ★★ ⚠ same type
CEP97 p.Arg585Cys Uncertain significance ★★ ⚠ same type
CEP97 p.Arg591Cys Uncertain significance ★★ ⚠ same type
CEP97 p.Arg615Cys 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/cep97-p-ser331arg (accessed [today's date]).

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