Is CEP131 p.Arg1004Trp (c.3010C>T) pathogenic?

CEP131 p.Arg1004Trp (c.3010C>T) is classified Uncertain significance in CEP131 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.1521); Very rare (popmax 0.0077%, sas).

How common is CEP131 p.Arg1004Trp (c.3010C>T) in the general population?

CEP131 p.Arg1004Trp (c.3010C>T) is very rare (popmax 0.0077%, sas) (gnomAD).

What do computational predictors say about CEP131 p.Arg1004Trp (c.3010C>T)?

AlphaMissense predicts likely benign (score 0.1521) — an in-silico prediction, not a clinical call.

CEP131 p.Arg1004Trp

c.3010C>T · VCV4225896

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1521 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0077%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1521	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -12.21	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP -1.6, phastCons 0.98
Regional constraint	o/e 1.06	unconstrained · MANE · 9,708 bp · p 0.047 · 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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R1007W vs ClinVar R1004W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0077% South Asian · 7/90,944 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00206% 30/1,459,182 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0077%	12,992
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,536
European (non-Finnish)	0.00178%	56,167
African / African-American	0.00133%	75,032

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.Arg1004Trp
Coding: c.3010C>T
MANE Select: NM_014984
Type: single nucleotide variant
Location: chr17:81190736 (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.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
CEP131 p.Ala436Glu 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-arg1004trp (accessed [today's date]).

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