Is CEP85 p.Thr98Ala (c.292A>G) pathogenic?

CEP85 p.Thr98Ala (c.292A>G) is classified Uncertain significance in CEP85 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). AlphaMissense: likely benign (0.1927); Ultra-rare (popmax 0.0203%, nfe).

How common is CEP85 p.Thr98Ala (c.292A>G) in the general population?

CEP85 p.Thr98Ala (c.292A>G) is ultra-rare (popmax 0.0203%, nfe) (gnomAD).

What do computational predictors say about CEP85 p.Thr98Ala (c.292A>G)?

AlphaMissense predicts likely benign (score 0.1927) — an in-silico prediction, not a clinical call.

CEP85 p.Thr98Ala

c.292A>G · VCV4001177

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1927 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0203%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1927	likely benign
REVEL	0.35	indeterminate
SaProt	LLR -6.00	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 38 kb · p 0.075 · regional, not allelic
Overall
CADD	25.3	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 0.0203% European (non-Finnish) · 239/1,180,032 alleles

Filtering AF 0.0181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0173%

Overall 0.0156% 252/1,614,000 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0203%	4,937
Remaining individualsnot grpmax-eligible	0.0128%	7,811
African / African-American	0.00401%	24,963
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
Admixed American	0.00167%	59,982

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: CEP85
Protein: p.Thr98Ala
Coding: c.292A>G
MANE Select: NM_001319944
Type: single nucleotide variant
Location: chr1:26255254 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.09 · 2 PDB
Residue 98: the 'disordered' region

Full CEP85 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP85 p.Ala176= Benign ★★ same type
CEP85 p.Leu405Phe Benign ★★ same type
CEP85 p.Ala374Pro Uncertain significance ★ ⚠ same type
CEP85 p.Ala396Thr Uncertain significance ★ ⚠ same type
CEP85 p.Ala399Ser Uncertain significance ★ ⚠ same type
CEP85 p.Ala656Val Uncertain significance ★ ⚠ same type
CEP85 p.Arg146Lys Uncertain significance ★ ⚠ same type
CEP85 p.Arg177Lys 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/cep85-p-thr98ala (accessed [today's date]).

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