Is ASPDH p.Val71Leu (c.211G>C) pathogenic?

ASPDH p.Val71Leu (c.211G>C) is classified Uncertain significance in ASPDH (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-28). AlphaMissense: ambiguous (0.482); Very rare (popmax 0.00017%, nfe).

How common is ASPDH p.Val71Leu (c.211G>C) in the general population?

ASPDH p.Val71Leu (c.211G>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about ASPDH p.Val71Leu (c.211G>C)?

AlphaMissense predicts ambiguous (score 0.482) — an in-silico prediction, not a clinical call.

ASPDH p.Val71Leu

c.211G>C · rs781096212 · VCV2286473

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.482 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Computational evidence

Protein change
AlphaMissense	0.482	ambiguous
REVEL	0.305	indeterminate
SaProt	LLR -9.45	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.1, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 2,090 bp · p 0.32 · regional, not allelic
Overall
CADD	26.0	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 0.00017% European (non-Finnish) · 2/1,179,692 alleles

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

Overall 0.000137% 2/1,461,158 alleles · very rare

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.Val71Leu
Coding: c.211G>C
MANE Select: NM_001114598
dbSNP: rs781096212
Type: single nucleotide variant
Location: chr19:50512998 (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.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
ASPDH p.Arg158Gln 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-val71leu (accessed [today's date]).

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