Is CEP131 p.Arg1061Trp (c.3181C>T) pathogenic?

CEP131 p.Arg1061Trp (c.3181C>T) is classified Uncertain significance in CEP131 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.3223); Ultra-rare (popmax 0.0227%, afr).

How common is CEP131 p.Arg1061Trp (c.3181C>T) in the general population?

CEP131 p.Arg1061Trp (c.3181C>T) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

What do computational predictors say about CEP131 p.Arg1061Trp (c.3181C>T)?

AlphaMissense predicts likely benign (score 0.3223) — an in-silico prediction, not a clinical call.

CEP131 p.Arg1061Trp

c.3181C>T · rs371210650 · VCV3142568

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3223 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3223	likely benign
REVEL	0.244	benign-leaning
SaProt	LLR -12.07	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 3.5	GERP -0.73, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 9,708 bp · p 0.047 · regional, not allelic
Overall
CADD	25.4	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 R1064W vs ClinVar R1061W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0227% African / African-American · 17/75,014 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.0085% 137/1,611,804 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,413
Middle Eastern	0.0167%	5,980
European (non-Finnish)	0.00907%	11,024
Remaining individualsnot grpmax-eligible	0.00801%	12,487
South Asian	0.00439%	22,753
Admixed American	0.00333%	29,999
East Asian	0.00223%	44,860

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.Arg1061Trp
Coding: c.3181C>T
MANE Select: NM_014984
dbSNP: rs371210650
Type: single nucleotide variant
Location: chr17:81189831 (GRCh38)
Gene constraint: LOEUF 1.031 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.20
Residue 1061: the 'disordered' region

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

Similar variants

CEP131 p.Arg1061Gln 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-arg1061trp (accessed [today's date]).

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