Is PHGDH p.Ala184= (c.552C>T) pathogenic?

PHGDH p.Ala184= (c.552C>T) is classified Likely benign in PHGDH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-17). Absent from gnomAD v4.1; Associated with PHGDH deficiency.

What condition is associated with PHGDH p.Ala184= (c.552C>T)?

PHGDH p.Ala184= (c.552C>T) is associated with PHGDH deficiency (ClinVar).

How common is PHGDH p.Ala184= (c.552C>T) in the general population?

PHGDH p.Ala184= (c.552C>T) is absent from gnomAD v4.1 (gnomAD).

PHGDH p.Ala184=

c.552C>T · rs761331510 · VCV1612423

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

PHGDH deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.071	GERP -3, phastCons 0.89
Overall
CADD	10.55	PHRED · no single calibrated threshold — expert panels disagree

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: PHGDH
Protein: p.Ala184=
Coding: c.552C>T
MANE Select: NM_006623
dbSNP: rs761331510
Type: single nucleotide variant
Location: chr1:119734675 (GRCh38)
Gene constraint: LOEUF 1.155 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.06 · 21 PDB
Residue 184: an α-helix

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.Ala184Thr Uncertain significance ★ ⚠ same residue
PHGDH c.1078+1G>A Likely pathogenic ★★ same condition
PHGDH c.138+1G>T Likely pathogenic ★★ same condition
PHGDH c.139-2A>G Likely pathogenic ★★ same condition
PHGDH c.290+2T>C Pathogenic/Likely pathogenic ★★ same condition
PHGDH c.357-1G>A Pathogenic/Likely pathogenic ★★ same condition
PHGDH c.412-1G>C Likely pathogenic ★★ same condition
PHGDH c.643+1G>A 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/phgdh-p-ala184 (accessed [today's date]).

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