Is CEP83 p.Leu137Pro (c.410T>C) pathogenic?

CEP83 p.Leu137Pro (c.410T>C) is classified Likely pathogenic in CEP83 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-02-04). AlphaMissense: likely pathogenic (0.9287); Very rare (popmax 0.00341%, sas).

How common is CEP83 p.Leu137Pro (c.410T>C) in the general population?

CEP83 p.Leu137Pro (c.410T>C) is very rare (popmax 0.00341%, sas) (gnomAD).

What do computational predictors say about CEP83 p.Leu137Pro (c.410T>C)?

AlphaMissense predicts likely pathogenic (score 0.9287) — an in-silico prediction, not a clinical call.

CEP83 p.Leu137Pro

c.410T>C · rs763352069 · VCV988364

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9287 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00341%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9287	likely pathogenic ✓ concordant with ClinVar · top 2% in CEP83
REVEL	0.663	pathogenic-leaning
SaProt	LLR -12.07	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 104 kb · p 0.01 · regional, not allelic
Overall
CADD	25.0	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 0.00341% South Asian · 3/87,856 alleles

Filtering AF 0.000907% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000452%

Overall 0.000589% 8/1,357,352 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00341%	29,285
Finnishnot grpmax-eligible	0.00314%	31,868
Remaining individualsnot grpmax-eligible	0.0017%	58,956
European (non-Finnish)	0.000184%	543,661

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: CEP83
Protein: p.Leu137Pro
Coding: c.410T>C
MANE Select: NM_016122
dbSNP: rs763352069
Type: single nucleotide variant
Location: chr12:94403177 (GRCh38)
Gene constraint: LOEUF 0.807 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.90

Full CEP83 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP83 p.Arg209Ter Pathogenic/Likely pathogenic ★★ same type
CEP83 p.Arg215Ter Pathogenic/Likely pathogenic ★★ same type
CEP83 p.Arg511Pro Pathogenic/Likely pathogenic ★★ same type
CEP83 p.Arg511Ter Pathogenic/Likely pathogenic ★★ same type
CEP83 p.Gln81Ter Pathogenic/Likely pathogenic ★★ same type
CEP83 p.Leu351Ter Pathogenic/Likely pathogenic ★★ same type
CEP83 p.Ala232Val Uncertain significance ★★ ⚠ same type
CEP83 p.Ala243Val 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/cep83-p-leu137pro (accessed [today's date]).

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