Is AASS p.Ser900Leu (c.2699C>T) pathogenic?

AASS p.Ser900Leu (c.2699C>T) is classified Likely benign in AASS (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-22). AlphaMissense: likely benign (0.0846); Ultra-rare (popmax 0.0911%, sas); Associated with Inborn genetic diseases.

What condition is associated with AASS p.Ser900Leu (c.2699C>T)?

AASS p.Ser900Leu (c.2699C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AASS p.Ser900Leu (c.2699C>T) in the general population?

AASS p.Ser900Leu (c.2699C>T) is ultra-rare (popmax 0.0911%, sas) (gnomAD).

What do computational predictors say about AASS p.Ser900Leu (c.2699C>T)?

AlphaMissense predicts likely benign (score 0.0846) — an in-silico prediction, not a clinical call.

AASS p.Ser900Leu

c.2699C>T · VCV4562646

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0846 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0911%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0846	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -9.29	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 7.5	GERP 1.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 57 kb · p 0.0048 · regional, not allelic
Overall
CADD	23.9	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 0.0911% South Asian · 83/91,074 alleles

Filtering AF 0.0752% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0694%

Overall 0.00564% 91/1,613,788 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0911%	1,097
Remaining individualsnot grpmax-eligible	0.0112%	8,929
European (non-Finnish)	8.48e-05%	1,179,792

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.Ser900Leu
Coding: c.2699C>T
MANE Select: NM_005763
Type: single nucleotide variant
Location: chr7:122076571 (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 900: 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.Ser900= Likely benign ★ 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-ser900leu (accessed [today's date]).

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