Is PRODH p.Tyr548= (c.1644C>T) pathogenic?

PRODH p.Tyr548= (c.1644C>T) is classified Likely benign in PRODH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). Ultra-rare (popmax 0.0164%, afr); Associated with hyperprolinemia type 1.

What condition is associated with PRODH p.Tyr548= (c.1644C>T)?

PRODH p.Tyr548= (c.1644C>T) is associated with hyperprolinemia type 1 (ClinVar).

How common is PRODH p.Tyr548= (c.1644C>T) in the general population?

PRODH p.Tyr548= (c.1644C>T) is ultra-rare (popmax 0.0164%, afr) (gnomAD).

How is Hyperprolinemia type 1 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PRODH p.Tyr548=

c.1644C>T · rs540773005 · VCV2892154

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, afr)

Conditions

hyperprolinemia type 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 -5.6	GERP -8.2
Overall
CADD	0.291	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% African / African-American · 5/30,482 alleles

Filtering AF 0.00641% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00417%

Overall 0.00128% 5/390,996 alleles · ultra-rare exomes 3/363,166 · genomes 2/27,830 · joint denominator

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: PRODH
Protein: p.Tyr548=
Coding: c.1644C>T
MANE Select: NM_016335
dbSNP: rs540773005
Type: single nucleotide variant
Location: chr22:18913334 (GRCh38)
Structure: AlphaFold pLDDT 85.29

Full PRODH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hyperprolinemia type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hyperprolinemia type 1 (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

PRODH c.1104+2T>C Likely pathogenic ★★ same condition
PRODH p.Gln59Ter Pathogenic/Likely pathogenic ★★ same condition
PRODH p.Tyr412Ter Pathogenic ★★ same condition
PRODH c.1427+4C>T Uncertain significance ★★ same condition
PRODH c.1615+1G>C Uncertain significance ★★ same condition
PRODH c.482+6G>A Uncertain significance ★★ same condition
PRODH c.929+3G>A Uncertain significance ★★ same condition
PRODH p.Ala140Thr Uncertain significance ★★ 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/prodh-p-tyr548 (accessed [today's date]).

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