Is CEP135 p.Ile689Val (c.2065A>G) pathogenic?

CEP135 p.Ile689Val (c.2065A>G) is classified Likely benign in CEP135 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-08). AlphaMissense: likely benign (0.0561); Rare (popmax 0.786%, afr).

How common is CEP135 p.Ile689Val (c.2065A>G) in the general population?

CEP135 p.Ile689Val (c.2065A>G) is rare (popmax 0.786%, afr) (gnomAD).

What do computational predictors say about CEP135 p.Ile689Val (c.2065A>G)?

AlphaMissense predicts likely benign (score 0.0561) — an in-silico prediction, not a clinical call.

CEP135 p.Ile689Val

c.2065A>G · rs139407231 · VCV434722

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0561 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.786%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0561	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -6.20	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 -2.9	GERP -3.2
Regional constraint	o/e 1.01	unconstrained · MANE · 72 kb · p 0.83 · regional, not allelic
Overall
CADD	0.018	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 0.786% African / African-American · 590/75,072 alleles

Filtering AF 0.733% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.713%

Overall 0.0422% 682/1,614,210 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.786%	127
Admixed American	0.0816%	1,225
Remaining individualsnot grpmax-eligible	0.0544%	1,838
Middle Eastern	0.0165%	6,062
South Asian	0.0022%	45,544
European (non-Finnish)	0.000508%	196,671

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: CEP135
Protein: p.Ile689Val
Coding: c.2065A>G
MANE Select: NM_025009
dbSNP: rs139407231
Type: single nucleotide variant
Location: chr4:55999357 (GRCh38)
Gene constraint: LOEUF 0.989 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.15 · 2 PDB

Full CEP135 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP135 c.473-1G>C Likely pathogenic ★★ same type
CEP135 p.Arg1083Ter Pathogenic/Likely pathogenic ★★ same type
CEP135 p.Arg292Ter Pathogenic/Likely pathogenic ★★ same type
CEP135 p.Arg418Ter Pathogenic ★★ same type
CEP135 p.Arg470Ter Pathogenic/Likely pathogenic ★★ same type
CEP135 p.Arg908Ter Pathogenic ★★ same type
CEP135 p.Leu578Ter Pathogenic ★★ same type
CEP135 p.Lys1071Ter 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/cep135-p-ile689val (accessed [today's date]).

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