Is AASDH p.Pro1024Leu (c.3071C>T) pathogenic?

AASDH p.Pro1024Leu (c.3071C>T) is classified Uncertain significance in AASDH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely pathogenic (0.5897); Ultra-rare (popmax 0.034%, sas).

How common is AASDH p.Pro1024Leu (c.3071C>T) in the general population?

AASDH p.Pro1024Leu (c.3071C>T) is ultra-rare (popmax 0.034%, sas) (gnomAD).

What do computational predictors say about AASDH p.Pro1024Leu (c.3071C>T)?

AlphaMissense predicts likely pathogenic (score 0.5897) — an in-silico prediction, not a clinical call.

AASDH p.Pro1024Leu

c.3071C>T · rs748897192 · VCV3141147

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5897 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.034%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5897	likely pathogenic
REVEL	0.738	pathogenic-leaning
SaProt	LLR -9.96	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 46 kb · p 0.076 · regional, not allelic
Overall
CADD	26.8	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 0.034% South Asian · 31/91,082 alleles

Filtering AF 0.0246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0214%

Overall 0.0026% 38/1,461,868 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.034%	2,938
East Asian	0.0111%	8,976
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)	8.47e-05%	1,180,020

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: AASDH
Protein: p.Pro1024Leu
Coding: c.3071C>T
MANE Select: NM_181806
dbSNP: rs748897192
Type: single nucleotide variant
Location: chr4:56338628 (GRCh38)
Gene constraint: LOEUF 0.946 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.50

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

Similar variants

AASDH p.Ile61Val Benign ★★ same type
AASDH p.Ala274Val Uncertain significance ★ ⚠ same type
AASDH p.Ala643Asp Uncertain significance ★ ⚠ same type
AASDH p.Ala643Thr Uncertain significance ★ ⚠ same type
AASDH p.Ala705Gly Uncertain significance ★ ⚠ same type
AASDH p.Ala878Thr Uncertain significance ★ ⚠ same type
AASDH p.Ala880Thr Uncertain significance ★ ⚠ same type
AASDH p.Arg1019Thr 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/aasdh-p-pro1024leu (accessed [today's date]).

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