PHGDH p.Arg268=
c.804G>A · rs587719252 · VCV752693
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0867%, sas)
Conditions
1
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 0.9 | GERP -2.6, phastCons 0.22 |
| Overall | ||
| CADD | 6.071 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0867%
South Asian · 79/91,080 alleles
Filtering AF
0.0713%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0657%
Overall
0.00589%
95/1,614,164 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0867% | 1,153 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,251 |
| East Asian | 0.00223% | 44,888 |
| African / African-American | 0.00133% | 75,062 |
| European (non-Finnish) | 0.00102% | 98,334 |
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.Arg268=
- Coding
- c.804G>A
- MANE Select
- NM_006623
- dbSNP
- rs587719252
- Type
- single nucleotide variant
- Location
- chr1:119737125 (GRCh38)
- Gene constraint
- LOEUF 1.155 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.06 · 21 PDB
Similar variants
- PHGDH p.Arg268Gln Uncertain significance ★★ ⚠ same residue
- PHGDH p.Arg268Trp 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
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-arg268 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown