Is CERT1 p.Phe19Val (c.55T>G) pathogenic?

CERT1 p.Phe19Val (c.55T>G) is classified Likely benign in CERT1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-10-14). Rare (popmax 0.234%, mid); Associated with intellectual disability, autosomal dominant 34.

What condition is associated with CERT1 p.Phe19Val (c.55T>G)?

CERT1 p.Phe19Val (c.55T>G) is associated with intellectual disability, autosomal dominant 34, intellectual disability (ClinVar).

How common is CERT1 p.Phe19Val (c.55T>G) in the general population?

CERT1 p.Phe19Val (c.55T>G) is rare (popmax 0.234%, mid) (gnomAD).

CERT1 p.Phe19Val

c.55T>G · rs202137230 · VCV975373

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.234%, mid)

Conditions

intellectual disability, autosomal dominant 34

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.003	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -3.3, phastCons 0.23
Overall
CADD	9.185	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.234% Middle Eastern · 14/5,980 alleles

Filtering AF 0.141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.113%

Overall 0.0222% 344/1,551,408 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.234%	427
Remaining individualsnot grpmax-eligible	0.0898%	1,113
Admixed American	0.0882%	1,133
European (non-Finnish)	0.0194%	5,143
African / African-American	0.00957%	10,447
Finnishnot grpmax-eligible	0.00167%	59,882

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.Phe19Val
Coding: c.55T>G
MANE Select: NM_001379029 · reported on NM_001130105
dbSNP: rs202137230
Type: single nucleotide variant
Location: chr5:75511790 (GRCh38)
Gene constraint: LOEUF 0.656 · pLI 0.10 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 77.75 · 27 PDB
Residue 19: the 'disordered' region

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

Also linked: intellectual disability

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 c.-114G>T Pathogenic ★ same condition
CERT1 p.Ala581Val Likely pathogenic ★ same condition
CERT1 p.Gly243Ala 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-phe19val (accessed [today's date]).

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