Is QDPR p.Ser99Phe (c.296C>T) pathogenic?

QDPR p.Ser99Phe (c.296C>T) is classified Uncertain significance in QDPR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-23). AlphaMissense: likely benign (0.3268); Very rare (popmax 0.0011%, sas).

How common is QDPR p.Ser99Phe (c.296C>T) in the general population?

QDPR p.Ser99Phe (c.296C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about QDPR p.Ser99Phe (c.296C>T)?

AlphaMissense predicts likely benign (score 0.3268) — an in-silico prediction, not a clinical call.

QDPR p.Ser99Phe

c.296C>T · VCV4966757

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3268 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3268	likely benign
REVEL	0.693	pathogenic-leaning
SaProt	LLR -13.78	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.5	GERP 2.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 25 kb · p 0.99 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,084 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,820 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,084
European (non-Finnish)	0.000169%	590,005

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: QDPR
Protein: p.Ser99Phe
Coding: c.296C>T
MANE Select: NM_000320
Type: single nucleotide variant
Location: chr4:17501859 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.43 · 2 PDB

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

Similar variants

QDPR p.Ser99= Conflicting classifications of pathogenicity ★ same residue
QDPR c.436+2552A>G Pathogenic ★★ same type
QDPR c.545+1G>A Pathogenic ★★ same type
QDPR c.546-1G>A Likely pathogenic ★★ same type
QDPR p.Arg221Ter Pathogenic ★★ same type
QDPR p.His158Tyr Pathogenic/Likely pathogenic ★★ same type
QDPR p.Phe212Ser Likely pathogenic ★★ same type
QDPR p.Ser115Leu Pathogenic/Likely pathogenic ★★ same type

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/qdpr-p-ser99phe (accessed [today's date]).

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