Is CEP152 p.Met41Val (c.121A>G) pathogenic?

CEP152 p.Met41Val (c.121A>G) is classified Uncertain significance in CEP152 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-13). AlphaMissense: ambiguous (0.5111); Very rare (popmax 0.00329%, sas).

How common is CEP152 p.Met41Val (c.121A>G) in the general population?

CEP152 p.Met41Val (c.121A>G) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about CEP152 p.Met41Val (c.121A>G)?

AlphaMissense predicts ambiguous (score 0.5111) — an in-silico prediction, not a clinical call.

CEP152 p.Met41Val

c.121A>G · VCV3336007

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5111 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5111	ambiguous
REVEL	0.188	benign-leaning
SaProt	LLR -5.31	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 7.9	GERP 5.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 67 kb · p 0.21 · regional, not allelic
Overall
CADD	24.7	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 0.00329% South Asian · 3/91,074 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000274% 4/1,461,762 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,358
Remaining individualsnot grpmax-eligible	0.0016%	62,504

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.Met41Val
Coding: c.121A>G
MANE Select: NM_001194998
Type: single nucleotide variant
Location: chr15:48798018 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.54 · 3 PDB
Residue 41: the 'interaction with plk4' region; the 'disordered' region

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

Similar variants

CEP152 c.1578-1G>A Likely pathogenic ★★ same type
CEP152 c.1908+1G>T Likely pathogenic ★★ same type
CEP152 c.540+1G>A Pathogenic/Likely pathogenic ★★ same type
CEP152 c.88-2A>G Likely pathogenic ★★ same type
CEP152 c.972+2T>A Likely pathogenic ★★ same type
CEP152 p.Arg115Ter Pathogenic/Likely pathogenic ★★ same type
CEP152 p.Arg1309Ter Pathogenic/Likely pathogenic ★★ same type
CEP152 p.Arg267Ter Pathogenic/Likely pathogenic ★★ 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/cep152-p-met41val (accessed [today's date]).

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