Is ASPDH p.Pro202Ser (c.604C>T) pathogenic?

ASPDH p.Pro202Ser (c.604C>T) is classified Uncertain significance in ASPDH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-07). AlphaMissense: likely benign (0.1265); Ultra-rare (popmax 0.0747%, sas).

How common is ASPDH p.Pro202Ser (c.604C>T) in the general population?

ASPDH p.Pro202Ser (c.604C>T) is ultra-rare (popmax 0.0747%, sas) (gnomAD).

What do computational predictors say about ASPDH p.Pro202Ser (c.604C>T)?

AlphaMissense predicts likely benign (score 0.1265) — an in-silico prediction, not a clinical call.

ASPDH p.Pro202Ser

c.604C>T · rs543505493 · VCV2472560

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1265 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0747%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1265	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	LLR -11.32	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.84, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 2,090 bp · p 0.32 · regional, not allelic
Overall
CADD	23.4	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 0.0747% South Asian · 68/91,028 alleles

Filtering AF 0.0604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0552%

Overall 0.00428% 69/1,612,580 alleles · ultra-rare exomes 65/1,460,274 · genomes 4/152,306 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0747%	1,339
Remaining individualsnot grpmax-eligible	0.0016%	62,344

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: ASPDH
Protein: p.Pro202Ser
Coding: c.604C>T
MANE Select: NM_001114598
dbSNP: rs543505493
Type: single nucleotide variant
Location: chr19:50512409 (GRCh38)
Gene constraint: LOEUF 1.216 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.88

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

Similar variants

ASPDH p.Pro202Ala Uncertain significance ★ ⚠ same residue
ASPDH p.Ala120Thr Uncertain significance ★ ⚠ same type
ASPDH p.Ala127Thr Uncertain significance ★ same type
ASPDH p.Ala139Glu Uncertain significance ★ ⚠ same type
ASPDH p.Ala187Val Uncertain significance ★ ⚠ same type
ASPDH p.Ala195Glu Uncertain significance ★ ⚠ same type
ASPDH p.Ala241Thr Uncertain significance ★ ⚠ same type
ASPDH p.Ala85Glu Uncertain significance ★ ⚠ 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/aspdh-p-pro202ser (accessed [today's date]).

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