Is CEP152 p.Val736Ala (c.2207T>C) pathogenic?

CEP152 p.Val736Ala (c.2207T>C) is classified Uncertain significance in CEP152 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-30). AlphaMissense: likely pathogenic (0.7368); Very rare (popmax 0.00833%, amr); Associated with Inborn genetic diseases.

What condition is associated with CEP152 p.Val736Ala (c.2207T>C)?

CEP152 p.Val736Ala (c.2207T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CEP152 p.Val736Ala (c.2207T>C) in the general population?

CEP152 p.Val736Ala (c.2207T>C) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about CEP152 p.Val736Ala (c.2207T>C)?

AlphaMissense predicts likely pathogenic (score 0.7368) — an in-silico prediction, not a clinical call.

CEP152 p.Val736Ala

c.2207T>C · rs767225850 · VCV1374752

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7368 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7368	likely pathogenic · top 7% in CEP152
REVEL	0.222	benign-leaning
SaProt	LLR -6.47	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 67 kb · p 0.21 · regional, not allelic
Overall
CADD	25.5	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 0.00833% Admixed American · 5/59,994 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000558% 9/1,613,650 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	11,999
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)	0.000254%	393,342

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.Val736Ala
Coding: c.2207T>C
MANE Select: NM_001194998
dbSNP: rs767225850
Type: single nucleotide variant
Location: chr15:48767133 (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-val736ala (accessed [today's date]).

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