Is CEP97 p.Phe856Leu (c.2566T>C) pathogenic?

CEP97 p.Phe856Leu (c.2566T>C) is classified Likely benign in CEP97 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: ambiguous (0.5522); Rare (popmax 0.324%, afr).

How common is CEP97 p.Phe856Leu (c.2566T>C) in the general population?

CEP97 p.Phe856Leu (c.2566T>C) is rare (popmax 0.324%, afr) (gnomAD).

What do computational predictors say about CEP97 p.Phe856Leu (c.2566T>C)?

AlphaMissense predicts ambiguous (score 0.5522) — an in-silico prediction, not a clinical call.

CEP97 p.Phe856Leu

c.2566T>C · rs145177008 · VCV2052826

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5522 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.324%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5522	ambiguous
REVEL	0.287	benign-leaning
SaProt	LLR -4.89	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 5.1	GERP 0.64, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 41 kb · p 0.018 · regional, not allelic
Overall
CADD	20.8	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 0.324% African / African-American · 243/75,056 alleles

Filtering AF 0.29% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.277%

Overall 0.0166% 268/1,613,142 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.324%	309
Admixed American	0.0267%	3,751
Middle Eastern	0.0165%	6,054
Remaining individualsnot grpmax-eligible	0.0128%	7,809

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.Phe856Leu
Coding: c.2566T>C
MANE Select: NM_024548
dbSNP: rs145177008
Type: single nucleotide variant
Location: chr3:101765519 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.89
Residue 856: the 'interaction with mphosph9' 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-phe856leu (accessed [today's date]).

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