Is ASPDH p.Leu26Phe (c.78G>C) pathogenic?

ASPDH p.Leu26Phe (c.78G>C) is classified Uncertain significance in ASPDH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-05). AlphaMissense: likely benign (0.1724); Absent from gnomAD v4.1.

How common is ASPDH p.Leu26Phe (c.78G>C) in the general population?

ASPDH p.Leu26Phe (c.78G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASPDH p.Leu26Phe (c.78G>C)?

AlphaMissense predicts likely benign (score 0.1724) — an in-silico prediction, not a clinical call.

ASPDH p.Leu26Phe

c.78G>C · VCV3436612

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1724 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1724	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -11.87	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.44 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.6	GERP -0.2, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 2,090 bp · p 0.32 · regional, not allelic
Overall
CADD	22.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ASPDH
Protein: p.Leu26Phe
Coding: c.78G>C
MANE Select: NM_001114598
Type: single nucleotide variant
Location: chr19:50513391 (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-leu26phe (accessed [today's date]).

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