Is CEP97 p.Leu558Phe (c.1674A>C) pathogenic?

CEP97 p.Leu558Phe (c.1674A>C) is classified Uncertain significance in CEP97 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely benign (0.1753); Absent from gnomAD v4.1.

How common is CEP97 p.Leu558Phe (c.1674A>C) in the general population?

CEP97 p.Leu558Phe (c.1674A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP97 p.Leu558Phe (c.1674A>C)?

AlphaMissense predicts likely benign (score 0.1753) — an in-silico prediction, not a clinical call.

CEP97 p.Leu558Phe

c.1674A>C · rs772220751 · VCV3143103

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1753 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1753	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -8.46	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 2.3	GERP -1.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 41 kb · p 0.018 · regional, not allelic
Overall
CADD	15.48	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CEP97
Protein: p.Leu558Phe
Coding: c.1674A>C
MANE Select: NM_024548
dbSNP: rs772220751
Type: single nucleotide variant
Location: chr3:101758280 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.89
Residue 558: the iq domain; the 'ccp110-binding' region

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

Similar variants

CEP97 p.Leu558= Likely benign ★ same residue
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

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-leu558phe (accessed [today's date]).

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