Is CERT1 p.Ile239Val (c.715A>G) pathogenic?

CERT1 p.Ile239Val (c.715A>G) is classified Uncertain significance in CERT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-27). AlphaMissense: likely benign (0.137); Absent from gnomAD v4.1; Associated with intellectual disability, autosomal dominant 34.

What condition is associated with CERT1 p.Ile239Val (c.715A>G)?

CERT1 p.Ile239Val (c.715A>G) is associated with intellectual disability, autosomal dominant 34 (ClinVar).

How common is CERT1 p.Ile239Val (c.715A>G) in the general population?

CERT1 p.Ile239Val (c.715A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CERT1 p.Ile239Val (c.715A>G)?

AlphaMissense predicts likely benign (score 0.137) — an in-silico prediction, not a clinical call.

CERT1 p.Ile239Val

c.715A>G · VCV4854476

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.137 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, autosomal dominant 34

Computational evidence

Protein change
AlphaMissense	0.137	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -5.93	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 7.9	GERP 2.8, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 94 kb · p 1.1e-13 · regional, not allelic
Overall
CADD	23.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CERT1
Protein: p.Ile239Val
Coding: c.715A>G
MANE Select: NM_001379029
Type: single nucleotide variant
Location: chr5:75416998 (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

intellectual disability, autosomal dominant 34 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CERT1 p.Ser135Phe Likely pathogenic ★★ same condition
CERT1 p.Thr166Ala Pathogenic/Likely pathogenic ★★ ⚠ same condition
CERT1 p.Asp80Asn Uncertain significance ★★ ⚠ same condition
CERT1 p.Val434Ile Uncertain significance ★★ ⚠ same condition
CERT1 p.Val506Ile Uncertain significance ★★ ⚠ same condition
CERT1 p.Phe19Val Likely benign ★★ same condition
CERT1 c.-114G>T Pathogenic ★ same condition
CERT1 p.Ala581Val Likely pathogenic ★ 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-ile239val (accessed [today's date]).

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