Is CERT1 p.Ser135Phe (c.404C>T) pathogenic?

CERT1 p.Ser135Phe (c.404C>T) is classified Likely pathogenic in CERT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-17). AlphaMissense: likely pathogenic (0.9742); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CERT1 p.Ser135Phe (c.404C>T)?

CERT1 p.Ser135Phe (c.404C>T) is associated with Inborn genetic diseases, intellectual disability, autosomal dominant 34 (ClinVar).

How common is CERT1 p.Ser135Phe (c.404C>T) in the general population?

CERT1 p.Ser135Phe (c.404C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CERT1 p.Ser135Phe (c.404C>T)?

AlphaMissense predicts likely pathogenic (score 0.9742) — an in-silico prediction, not a clinical call.

CERT1 p.Ser135Phe

c.404C>T · rs1763619016 · VCV985122

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9742 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9742	likely pathogenic ✓ concordant with ClinVar
REVEL	0.669	pathogenic-leaning
SaProt	LLR -13.77	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 94 kb · p 1.1e-13 · regional, not allelic
Overall
CADD	33.0	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

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.Ser135Phe
Coding: c.404C>T
MANE Select: NM_001379029
dbSNP: rs1763619016
Type: single nucleotide variant
Location: chr5:75426423 (GRCh38)
Gene constraint: LOEUF 0.656 · pLI 0.10 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 77.75 · 27 PDB
Residue 135: a modified residue (phosphoserine)

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

Also linked: intellectual disability, autosomal dominant 34

Similar variants

CERT1 p.Thr166Ala Pathogenic/Likely pathogenic ★★ ⚠ same condition
CERT1 c.-195C>T Uncertain significance ★★ same condition
CERT1 p.Ala538Val Uncertain significance ★★ ⚠ same condition
CERT1 p.Asp80Asn 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 p.Val434Ile 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/cert1-p-ser135phe (accessed [today's date]).

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