Is CEP104 p.Ala736Val (c.2207C>T) pathogenic?

CEP104 p.Ala736Val (c.2207C>T) is classified Uncertain significance in CEP104 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely benign (0.0747); Ultra-rare (popmax 0.01%, amr); Associated with Inborn genetic diseases.

What condition is associated with CEP104 p.Ala736Val (c.2207C>T)?

CEP104 p.Ala736Val (c.2207C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CEP104 p.Ala736Val (c.2207C>T) in the general population?

CEP104 p.Ala736Val (c.2207C>T) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about CEP104 p.Ala736Val (c.2207C>T)?

AlphaMissense predicts likely benign (score 0.0747) — an in-silico prediction, not a clinical call.

CEP104 p.Ala736Val

c.2207C>T · VCV4612216

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0747 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0747	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -7.12	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 3	GERP 0.65, phastCons 0.93
Regional constraint	o/e 0.91	unconstrained · MANE · 37 kb · p 0.0023 · regional, not allelic
Overall
CADD	14.34	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 0.01% Admixed American · 6/59,992 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000434% 7/1,613,572 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,999
African / African-American	0.00133%	74,910

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: CEP104
Protein: p.Ala736Val
Coding: c.2207C>T
MANE Select: NM_014704
Type: single nucleotide variant
Location: chr1:3826418 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.75 · 2 PDB
Residue 736: a UniProt-annotated variant site (in mrt77)

Full CEP104 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

CEP104 p.Ala269Thr Uncertain significance ★★ ⚠ same condition
CEP104 p.Ala499Thr Uncertain significance ★★ ⚠ same condition
CEP104 p.Ala629Val Uncertain significance ★★ ⚠ same condition
CEP104 p.Arg111Gln Uncertain significance ★★ ⚠ same condition
CEP104 p.Arg22Gln Uncertain significance ★★ ⚠ same condition
CEP104 p.Arg299Gln Uncertain significance ★★ ⚠ same condition
CEP104 p.Arg382Gln Uncertain significance ★★ ⚠ same condition
CEP104 p.Arg388His 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/cep104-p-ala736val (accessed [today's date]).

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