Is PHGDH p.Ser183= (c.549G>A) pathogenic?

PHGDH p.Ser183= (c.549G>A) is classified Likely benign in PHGDH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). Ultra-rare (popmax 0.0242%, sas); Associated with PHGDH deficiency.

What condition is associated with PHGDH p.Ser183= (c.549G>A)?

PHGDH p.Ser183= (c.549G>A) is associated with PHGDH deficiency (ClinVar).

How common is PHGDH p.Ser183= (c.549G>A) in the general population?

PHGDH p.Ser183= (c.549G>A) is ultra-rare (popmax 0.0242%, sas) (gnomAD).

PHGDH p.Ser183=

c.549G>A · rs776140200 · VCV1142306

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0242%, sas)

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 -7	GERP -3
Overall
CADD	1.691	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0242% South Asian · 22/91,074 alleles

Filtering AF 0.0163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.00223% 36/1,613,834 alleles · ultra-rare exomes 26/1,461,774 · genomes 10/152,060 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0242%	4,140
African / African-American	0.0107%	9,358
Finnishnot grpmax-eligible	0.00469%	21,336
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.00017%	589,953

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.Ser183=
Coding: c.549G>A
MANE Select: NM_006623
dbSNP: rs776140200
Type: single nucleotide variant
Location: chr1:119734672 (GRCh38)
Gene constraint: LOEUF 1.155 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.06 · 21 PDB
Residue 183: 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.Ser183Leu Uncertain significance ★★ ⚠ same residue
PHGDH p.Ser183Pro 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-ser183 (accessed [today's date]).

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