Is CEP97 p.Glu623Ala (c.1868A>C) pathogenic?

CEP97 p.Glu623Ala (c.1868A>C) is classified Uncertain significance in CEP97 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-13). AlphaMissense: ambiguous (0.4126); Ultra-rare (popmax 0.0165%, mid).

How common is CEP97 p.Glu623Ala (c.1868A>C) in the general population?

CEP97 p.Glu623Ala (c.1868A>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CEP97 p.Glu623Ala (c.1868A>C)?

AlphaMissense predicts ambiguous (score 0.4126) — an in-silico prediction, not a clinical call.

CEP97 p.Glu623Ala

c.1868A>C · rs375618960 · VCV2527871

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4126 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Computational evidence

Protein change
AlphaMissense	0.4126	ambiguous
REVEL	0.509	indeterminate
SaProt	LLR -8.46	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 41 kb · p 0.018 · regional, not allelic
Overall
CADD	27.0	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 0.0165% Middle Eastern · 1/6,046 alleles

Filtering AF 0.00923% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00723%

Overall 0.000807% 13/1,610,908 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,046
African / African-American	0.0161%	6,229

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.Glu623Ala
Coding: c.1868A>C
MANE Select: NM_024548
dbSNP: rs375618960
Type: single nucleotide variant
Location: chr3:101762535 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.89
Residue 623: the 'ccp110-binding' region; 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-glu623ala (accessed [today's date]).

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