Is AASS p.Met1Ile (c.3G>A) pathogenic?

AASS p.Met1Ile (c.3G>A) is classified Likely pathogenic in AASS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-24). Very rare (popmax 0.000593%, nfe); Associated with hyperlysinemia.

What condition is associated with AASS p.Met1Ile (c.3G>A)?

AASS p.Met1Ile (c.3G>A) is associated with hyperlysinemia (ClinVar).

How common is AASS p.Met1Ile (c.3G>A) in the general population?

AASS p.Met1Ile (c.3G>A) is very rare (popmax 0.000593%, nfe) (gnomAD).

How is Hyperlysinemia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AASS p.Met1Ile

c.3G>A · rs779793755 · VCV1048521

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Conditions

hyperlysinemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.338	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Overall
CADD	23.1	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 0.000593% European (non-Finnish) · 7/1,179,994 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000684% 10/1,461,774 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,256
Finnishnot grpmax-eligible	0.00156%	63,950
European (non-Finnish)grpmax	0.000593%	168,571

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Met1Ile
Coding: c.3G>A
MANE Select: NM_005763
dbSNP: rs779793755
Type: single nucleotide variant
Location: chr7:122133724 (GRCh38)
Gene constraint: LOEUF 0.948 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.73 · 9 PDB

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

Disease context

hyperlysinemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hyperlysinemia (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

AASS c.1767-1G>A Pathogenic/Likely pathogenic ★★ same condition
AASS p.Arg132His Likely pathogenic ★★ same condition
AASS p.Arg132Cys Uncertain significance ★★ ⚠ same condition
AASS p.Gln921Arg Uncertain significance ★★ ⚠ same condition
AASS p.Leu465Val Uncertain significance ★★ ⚠ same condition
AASS p.Lys780Thr Uncertain significance ★★ ⚠ same condition
AASS p.Tyr578Cys Uncertain significance ★★ ⚠ same condition
AASS p.Val350Met 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-met1ile (accessed [today's date]).

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