Is AASS p.Arg910Pro (c.2729G>C) pathogenic?

AASS p.Arg910Pro (c.2729G>C) is classified Uncertain significance in AASS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-18). AlphaMissense: likely pathogenic (0.889); Very rare (popmax 0.00229%, nfe).

How common is AASS p.Arg910Pro (c.2729G>C) in the general population?

AASS p.Arg910Pro (c.2729G>C) is very rare (popmax 0.00229%, nfe) (gnomAD).

What do computational predictors say about AASS p.Arg910Pro (c.2729G>C)?

AlphaMissense predicts likely pathogenic (score 0.889) — an in-silico prediction, not a clinical call.

AASS p.Arg910Pro

c.2729G>C · VCV3899536

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.889 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00229%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.889	likely pathogenic
REVEL	0.237	benign-leaning
SaProt	LLR -16.26	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 0.66, phastCons 0.002
Regional constraint	o/e 0.92	unconstrained · MANE · 57 kb · p 0.0048 · regional, not allelic
Overall
CADD	22.5	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 0.00229% European (non-Finnish) · 27/1,179,814 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.0018% 29/1,613,726 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00229%	43,697
Remaining individualsnot grpmax-eligible	0.0016%	62,476
Finnishnot grpmax-eligible	0.00156%	63,988

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.Arg910Pro
Coding: c.2729G>C
MANE Select: NM_005763
Type: single nucleotide variant
Location: chr7:122076541 (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 910: an α-helix; the 'saccharopine dehydrogenase' region

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

Similar variants

AASS p.Arg910Gln Uncertain significance ★ ⚠ same residue
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

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-arg910pro (accessed [today's date]).

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