Is AASS p.Gln810Ter (c.2428C>T) pathogenic?

AASS p.Gln810Ter (c.2428C>T) is classified Likely pathogenic in AASS (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-14). Very rare (popmax 0.00333%, amr).

How common is AASS p.Gln810Ter (c.2428C>T) in the general population?

AASS p.Gln810Ter (c.2428C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

AASS p.Gln810Ter

c.2428C>T · rs1027015345 · VCV2663547

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 22 of 24
Splicing
SpliceAI	Δ0.39	acceptor loss · deltas
Pangolin	Δ0.57	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.5	GERP 0.58, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,000 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000867% 14/1,614,036 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,000
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.000932%	107,277

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.Gln810Ter
Coding: c.2428C>T
MANE Select: NM_005763
dbSNP: rs1027015345
Type: single nucleotide variant
Location: chr7:122078919 (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 810: an α-helix; the 'saccharopine dehydrogenase' region

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

Similar variants

AASS c.1767-1G>A Pathogenic/Likely pathogenic ★★ same type
AASS p.Arg132His Likely pathogenic ★★ same type
AASS p.Arg132Cys Uncertain significance ★★ ⚠ same type
AASS p.Arg146Trp Uncertain significance ★★ ⚠ same type
AASS p.Asn34Lys Uncertain significance ★★ ⚠ same type
AASS p.Asn865Ser Uncertain significance ★★ ⚠ same type
AASS p.Gln921Arg Uncertain significance ★★ ⚠ same type
AASS p.Gly167Cys 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/aass-p-gln810ter (accessed [today's date]).

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