Is AASS p.Val823Asp (c.2468T>A) pathogenic?

AASS p.Val823Asp (c.2468T>A) is classified Uncertain significance in AASS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely benign (0.1583); Ultra-rare (popmax 0.0604%, sas); Associated with Inborn genetic diseases.

What condition is associated with AASS p.Val823Asp (c.2468T>A)?

AASS p.Val823Asp (c.2468T>A) is associated with Inborn genetic diseases (ClinVar).

How common is AASS p.Val823Asp (c.2468T>A) in the general population?

AASS p.Val823Asp (c.2468T>A) is ultra-rare (popmax 0.0604%, sas) (gnomAD).

What do computational predictors say about AASS p.Val823Asp (c.2468T>A)?

AlphaMissense predicts likely benign (score 0.1583) — an in-silico prediction, not a clinical call.

AASS p.Val823Asp

c.2468T>A · rs574621404 · VCV2596874

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1583 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0604%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1583	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -9.11	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 1.7	GERP 0.65, phastCons 0.89
Regional constraint	o/e 0.92	unconstrained · MANE · 57 kb · p 0.0048 · regional, not allelic
Overall
CADD	18.87	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 0.0604% South Asian · 55/91,082 alleles

Filtering AF 0.0476% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.043%

Overall 0.00347% 56/1,614,058 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0604%	1,656
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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: AASS
Protein: p.Val823Asp
Coding: c.2468T>A
MANE Select: NM_005763
dbSNP: rs574621404
Type: single nucleotide variant
Location: chr7:122078879 (GRCh38)
Gene constraint: LOEUF 0.948 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.73 · 9 PDB
Residue 823: an α-helix; the 'saccharopine dehydrogenase' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AASS p.Val823Ile Uncertain significance ★ ⚠ same residue
AASS p.Asn34Lys Uncertain significance ★★ ⚠ same condition
AASS p.Asn865Ser Uncertain significance ★★ ⚠ same condition
AASS p.Gly167Cys Uncertain significance ★★ ⚠ same condition
AASS p.His846Arg Uncertain significance ★★ ⚠ same condition
AASS p.Ile491Met Uncertain significance ★★ ⚠ same condition
AASS p.Leu465Val Uncertain significance ★★ ⚠ same condition
AASS p.Ser474Leu Uncertain significance ★★ ⚠ same condition

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/aass-p-val823asp (accessed [today's date]).

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