Is CEP131 p.Arg790Gln (c.2369G>A) pathogenic?

CEP131 p.Arg790Gln (c.2369G>A) is classified Uncertain significance in CEP131 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely benign (0.1155); Ultra-rare (popmax 0.0505%, sas).

How common is CEP131 p.Arg790Gln (c.2369G>A) in the general population?

CEP131 p.Arg790Gln (c.2369G>A) is ultra-rare (popmax 0.0505%, sas) (gnomAD).

What do computational predictors say about CEP131 p.Arg790Gln (c.2369G>A)?

AlphaMissense predicts likely benign (score 0.1155) — an in-silico prediction, not a clinical call.

CEP131 p.Arg790Gln

c.2369G>A · rs376522416 · VCV2515923

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1155 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0505%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1155	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -8.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 1, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 9,708 bp · p 0.047 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R793Q vs ClinVar R790Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0505% South Asian · 46/91,016 alleles

Filtering AF 0.0389% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0348%

Overall 0.00682% 109/1,597,670 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0505%	1,979
African / African-American	0.00934%	10,712
Remaining individualsnot grpmax-eligible	0.00803%	12,447
East Asian	0.00446%	22,427
European (non-Finnish)	0.00407%	24,548
Finnishnot grpmax-eligible	0.002%	50,062

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: CEP131
Protein: p.Arg790Gln
Coding: c.2369G>A
MANE Select: NM_014984
dbSNP: rs376522416
Type: single nucleotide variant
Location: chr17:81192796 (GRCh38)
Gene constraint: LOEUF 1.031 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.20

Full CEP131 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP131 p.Arg790Trp Uncertain significance ★ ⚠ same residue
CEP131 p.Pro365Ser Uncertain significance ★★ ⚠ same type
CEP131 p.Ala1024Thr Uncertain significance ★ ⚠ same type
CEP131 p.Ala1042Ser Uncertain significance ★ ⚠ same type
CEP131 p.Ala113Pro Uncertain significance ★ ⚠ same type
CEP131 p.Ala271Pro Uncertain significance ★ ⚠ same type
CEP131 p.Ala332Ser Uncertain significance ★ ⚠ same type
CEP131 p.Ala403Val 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/cep131-p-arg790gln (accessed [today's date]).

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