Is CEP135 p.Glu705Asp (c.2115G>T) pathogenic?

CEP135 p.Glu705Asp (c.2115G>T) is classified Likely benign in CEP135 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-27). AlphaMissense: likely benign (0.1868); Rare (popmax 0.814%, eas).

How common is CEP135 p.Glu705Asp (c.2115G>T) in the general population?

CEP135 p.Glu705Asp (c.2115G>T) is rare (popmax 0.814%, eas) (gnomAD).

What do computational predictors say about CEP135 p.Glu705Asp (c.2115G>T)?

AlphaMissense predicts likely benign (score 0.1868) — an in-silico prediction, not a clinical call.

CEP135 p.Glu705Asp

c.2115G>T · rs192298126 · VCV714476

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1868 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.814%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1868	likely benign
REVEL	0.123	moderately benign-leaning
SaProt	LLR -9.67	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 0.48	GERP -1.7, phastCons 0.4
Regional constraint	o/e 1.01	unconstrained · MANE · 72 kb · p 0.83 · regional, not allelic
Overall
CADD	18.65	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 0.814% East Asian · 365/44,856 alleles

Filtering AF 0.745% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.718%

Overall 0.0232% 375/1,613,728 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.814%	123
Remaining individualsnot grpmax-eligible	0.0128%	7,812
South Asian	0.0022%	45,465

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.Glu705Asp
Coding: c.2115G>T
MANE Select: NM_025009
dbSNP: rs192298126
Type: single nucleotide variant
Location: chr4:55999407 (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 p.Glu705Gly Uncertain significance ★★ ⚠ same residue
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

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-glu705asp (accessed [today's date]).

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