PHGDH p.Pro208=
c.624T>C · rs77401816 · VCV292313
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.22%, afr)
Conditions
2
Neu-Laxova syndrome 1
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 -0.19 | GERP 0.4, phastCons 0.61 |
| Overall | ||
| CADD | 8.304 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.22%
African / African-American · 1,662/74,944 alleles
Filtering AF
2.13%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.09%
Overall
0.113%
1,829/1,613,846 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.22% | 45 |
| Remaining individualsnot grpmax-eligible | 0.133% | 753 |
| Admixed American | 0.09% | 1,111 |
| Middle Eastern | 0.0825% | 1,212 |
| South Asian | 0.00769% | 13,007 |
| European (non-Finnish) | 0.00153% | 65,552 |
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.Pro208=
- Coding
- c.624T>C
- MANE Select
- NM_006623
- dbSNP
- rs77401816
- Type
- single nucleotide variant
- Location
- chr1:119734747 (GRCh38)
- Gene constraint
- LOEUF 1.155 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.06 · 21 PDB
Similar variants
- 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
- PHGDH p.Arg135Trp 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-pro208 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown