Is CERT1 p.Val267Ala (c.800T>C) pathogenic?

CERT1 p.Val267Ala (c.800T>C) is classified Uncertain significance in CERT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-03). AlphaMissense: likely benign (0.2146); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with CERT1 p.Val267Ala (c.800T>C)?

CERT1 p.Val267Ala (c.800T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CERT1 p.Val267Ala (c.800T>C) in the general population?

CERT1 p.Val267Ala (c.800T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CERT1 p.Val267Ala (c.800T>C)?

AlphaMissense predicts likely benign (score 0.2146) — an in-silico prediction, not a clinical call.

CERT1 p.Val267Ala

c.800T>C · rs1763155669 · VCV3143191

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2146 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2146	likely benign
REVEL	0.109	moderately benign-leaning
SaProt	LLR -2.55	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 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 5,845 bp · p 0.0028 · regional, not allelic
Overall
CADD	23.5	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 0.00133% African / African-American · 1/74,978 alleles

Overall 6.85e-05% 1/1,460,318 alleles · very rare

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: CERT1
Protein: p.Val267Ala
Coding: c.800T>C
MANE Select: NM_001379029
dbSNP: rs1763155669
Type: single nucleotide variant
Location: chr5:75416913 (GRCh38)
Gene constraint: LOEUF 0.656 · pLI 0.10 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 77.75 · 27 PDB

Full CERT1 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

CERT1 p.Ser135Phe Likely pathogenic ★★ same condition
CERT1 c.-195C>T Uncertain significance ★★ same condition
CERT1 p.Ala538Val Uncertain significance ★★ ⚠ same condition
CERT1 p.Cys185Phe Uncertain significance ★★ ⚠ same condition
CERT1 p.Gly452Asp Uncertain significance ★★ ⚠ same condition
CERT1 p.Met133Val Uncertain significance ★★ ⚠ same condition
CERT1 c.-140C>T Likely benign ★★ same condition
CERT1 p.Ile489Val Likely benign ★★ 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/cert1-p-val267ala (accessed [today's date]).

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