Is PHGDH p.Ala428fs (c.1282del) pathogenic?

PHGDH p.Ala428fs (c.1282del) is classified Pathogenic in PHGDH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-08). Absent from gnomAD; Associated with PHGDH deficiency.

What condition is associated with PHGDH p.Ala428fs (c.1282del)?

PHGDH p.Ala428fs (c.1282del) is associated with PHGDH deficiency (ClinVar).

How common is PHGDH p.Ala428fs (c.1282del) in the general population?

PHGDH p.Ala428fs (c.1282del) is absent from gnomAD (gnomAD).

PHGDH p.Ala428fs

c.1282del · rs2464203420 · VCV2849689

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

PHGDH deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PHGDH
Protein: p.Ala428fs
Coding: c.1282del
MANE Select: NM_006623
dbSNP: rs2464203420
Type: Deletion
Location: chr1:119742878 (GRCh38)
Gene constraint: LOEUF 1.155 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.06 · 21 PDB

Full PHGDH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PHGDH deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PHGDH p.Ala428= Likely benign ★ same residue
PHGDH p.Leu465fs Pathogenic/Likely pathogenic ★★ same condition
PHGDH p.Lys58fs Pathogenic/Likely pathogenic ★★ same condition
PHGDH p.Pro331fs Pathogenic/Likely pathogenic ★★ same condition
PHGDH p.Val301fs Pathogenic/Likely pathogenic ★★ same condition
PHGDH p.Ala320fs Pathogenic ★ same condition
PHGDH p.Gln123fs Pathogenic ★ same condition
PHGDH p.Glu297fs 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/phgdh-p-ala428fs (accessed [today's date]).

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