Is CEP152 p.His697Arg (c.2090A>G) pathogenic?

CEP152 p.His697Arg (c.2090A>G) is classified Uncertain significance in CEP152 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-10). AlphaMissense: ambiguous (0.4019); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with CEP152 p.His697Arg (c.2090A>G)?

CEP152 p.His697Arg (c.2090A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CEP152 p.His697Arg (c.2090A>G) in the general population?

CEP152 p.His697Arg (c.2090A>G) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CEP152 p.His697Arg (c.2090A>G)?

AlphaMissense predicts ambiguous (score 0.4019) — an in-silico prediction, not a clinical call.

CEP152 p.His697Arg

c.2090A>G · rs774173743 · VCV434737

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4019 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4019	ambiguous
REVEL	0.248	benign-leaning
SaProt	LLR -10.18	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 67 kb · p 0.21 · regional, not allelic
Overall
CADD	24.8	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000434% 7/1,614,102 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.00133%	74,944
European (non-Finnish)	0.000424%	236,008

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: CEP152
Protein: p.His697Arg
Coding: c.2090A>G
MANE Select: NM_001194998
dbSNP: rs774173743
Type: single nucleotide variant
Location: chr15:48767392 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.54 · 3 PDB

Full CEP152 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP152 c.540+6G>A Uncertain significance ★★ same condition
CEP152 p.Ala165Gly Uncertain significance ★★ ⚠ same condition
CEP152 p.Ala411Thr Uncertain significance ★★ ⚠ same condition
CEP152 p.Ala956Val Uncertain significance ★★ ⚠ same condition
CEP152 p.Arg1034Gln Uncertain significance ★★ ⚠ same condition
CEP152 p.Arg1283Cys Uncertain significance ★★ ⚠ same condition
CEP152 p.Arg1283His Uncertain significance ★★ ⚠ same condition
CEP152 p.Arg1312His Uncertain significance ★★ ⚠ same condition

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/cep152-p-his697arg (accessed [today's date]).

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