Is AASDH p.Pro1064Ser (c.3190C>T) pathogenic?

AASDH p.Pro1064Ser (c.3190C>T) is classified Uncertain significance in AASDH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-24). AlphaMissense: likely benign (0.2096); Ultra-rare (popmax 0.0167%, amr).

How common is AASDH p.Pro1064Ser (c.3190C>T) in the general population?

AASDH p.Pro1064Ser (c.3190C>T) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

What do computational predictors say about AASDH p.Pro1064Ser (c.3190C>T)?

AlphaMissense predicts likely benign (score 0.2096) — an in-silico prediction, not a clinical call.

AASDH p.Pro1064Ser

c.3190C>T · rs562650137 · VCV2598373

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2096 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2096	likely benign
REVEL	0.257	benign-leaning
SaProt	LLR -7.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 46 kb · p 0.076 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Admixed American · 10/59,976 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00682%

Overall 0.00316% 51/1,613,958 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	5,998
African / African-American	0.00533%	18,755
East Asian	0.00446%	22,432
Remaining individualsnot grpmax-eligible	0.0032%	31,250
European (non-Finnish)	0.0028%	35,758

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.Pro1064Ser
Coding: c.3190C>T
MANE Select: NM_181806
dbSNP: rs562650137
Type: single nucleotide variant
Location: chr4:56338509 (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-pro1064ser (accessed [today's date]).

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