Is CEP135 p.Ala950Thr (c.2848G>A) pathogenic?

CEP135 p.Ala950Thr (c.2848G>A) is classified Uncertain significance in CEP135 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.0753); Ultra-rare (popmax 0.0509%, mid); Associated with Inborn genetic diseases.

What condition is associated with CEP135 p.Ala950Thr (c.2848G>A)?

CEP135 p.Ala950Thr (c.2848G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CEP135 p.Ala950Thr (c.2848G>A) in the general population?

CEP135 p.Ala950Thr (c.2848G>A) is ultra-rare (popmax 0.0509%, mid) (gnomAD).

What do computational predictors say about CEP135 p.Ala950Thr (c.2848G>A)?

AlphaMissense predicts likely benign (score 0.0753) — an in-silico prediction, not a clinical call.

CEP135 p.Ala950Thr

c.2848G>A · rs766916059 · VCV2557237

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0753 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0509%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0753	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -4.06	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 -0.87, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 72 kb · p 0.83 · regional, not allelic
Overall
CADD	17.58	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0509% Middle Eastern · 3/5,894 alleles

Filtering AF 0.0139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00738%

Overall 0.00105% 17/1,613,318 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0509%	1,965
African / African-American	0.00267%	37,442
European (non-Finnish)	0.00102%	98,321

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.Ala950Thr
Coding: c.2848G>A
MANE Select: NM_025009
dbSNP: rs766916059
Type: single nucleotide variant
Location: chr4:56017693 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP135 p.Leu578Ter Pathogenic ★★ same condition
CEP135 c.2617-3C>T Uncertain significance ★★ same condition
CEP135 p.Ala1038Gly Uncertain significance ★★ ⚠ same condition
CEP135 p.Arg1116Gln Uncertain significance ★★ ⚠ same condition
CEP135 p.Arg168Cys Uncertain significance ★★ ⚠ same condition
CEP135 p.Arg252Trp Uncertain significance ★★ ⚠ same condition
CEP135 p.Arg435Cys Uncertain significance ★★ ⚠ same condition
CEP135 p.Arg442His Uncertain significance ★★ ⚠ same condition

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-ala950thr (accessed [today's date]).

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