Is CEP95 p.Ser806Pro (c.2416T>C) pathogenic?

CEP95 p.Ser806Pro (c.2416T>C) is classified Uncertain significance in CEP95 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-03). AlphaMissense: likely pathogenic (0.8192); Ultra-rare (popmax 0.0373%, afr).

How common is CEP95 p.Ser806Pro (c.2416T>C) in the general population?

CEP95 p.Ser806Pro (c.2416T>C) is ultra-rare (popmax 0.0373%, afr) (gnomAD).

What do computational predictors say about CEP95 p.Ser806Pro (c.2416T>C)?

AlphaMissense predicts likely pathogenic (score 0.8192) — an in-silico prediction, not a clinical call.

CEP95 p.Ser806Pro

c.2416T>C · VCV3490957

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8192 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0373%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8192	likely pathogenic · top 8% in CEP95
REVEL	0.084	moderately benign-leaning
SaProt	LLR -12.27	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -1.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 31 kb · p 0.11 · regional, not allelic
Overall
CADD	20.8	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 0.0373% African / African-American · 28/75,042 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0229%

Overall 0.0023% 37/1,611,678 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0373%	2,680
Remaining individualsnot grpmax-eligible	0.00801%	12,480
Admixed American	0.0067%	14,916

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: CEP95
Protein: p.Ser806Pro
Coding: c.2416T>C
MANE Select: NM_138363
Type: single nucleotide variant
Location: chr17:64537729 (GRCh38)
Gene constraint: LOEUF 1.061 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.70

Full CEP95 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP95 p.Ala188Val Uncertain significance ★ ⚠ same type
CEP95 p.Ala2Thr Uncertain significance ★ ⚠ same type
CEP95 p.Ala592Glu Uncertain significance ★ ⚠ same type
CEP95 p.Ala601Ser Uncertain significance ★ ⚠ same type
CEP95 p.Ala601Thr Uncertain significance ★ ⚠ same type
CEP95 p.Ala679Val Uncertain significance ★ ⚠ same type
CEP95 p.Arg134Gln Uncertain significance ★ ⚠ same type
CEP95 p.Arg183Gly 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/cep95-p-ser806pro (accessed [today's date]).

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