Is PHGDH p.Arg294= (c.882C>T) pathogenic?

PHGDH p.Arg294= (c.882C>T) is classified Likely benign in PHGDH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-06). Very rare (popmax 0.00333%, amr); Associated with PHGDH deficiency.

What condition is associated with PHGDH p.Arg294= (c.882C>T)?

PHGDH p.Arg294= (c.882C>T) is associated with PHGDH deficiency (ClinVar).

How common is PHGDH p.Arg294= (c.882C>T) in the general population?

PHGDH p.Arg294= (c.882C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

PHGDH p.Arg294=

c.882C>T · rs778794269 · VCV798006

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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 0.84	GERP 0.57, phastCons 1
Overall
CADD	10.21	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,024 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000137% 2/1,461,818 alleles · very rare

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: PHGDH
Protein: p.Arg294=
Coding: c.882C>T
MANE Select: NM_006623
dbSNP: rs778794269
Type: single nucleotide variant
Location: chr1:119737203 (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.Arg294Cys Uncertain significance ★★ ⚠ same residue
PHGDH p.Arg294His Uncertain significance ★ ⚠ same residue
PHGDH p.Arg294Leu 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

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-arg294 (accessed [today's date]).

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