Is AASS p.Arg471Cys (c.1411C>T) pathogenic?

AASS p.Arg471Cys (c.1411C>T) is classified Likely benign in AASS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-04). AlphaMissense: likely benign (0.1147); Ultra-rare (popmax 0.0226%, sas); Associated with Inborn genetic diseases.

What condition is associated with AASS p.Arg471Cys (c.1411C>T)?

AASS p.Arg471Cys (c.1411C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AASS p.Arg471Cys (c.1411C>T) in the general population?

AASS p.Arg471Cys (c.1411C>T) is ultra-rare (popmax 0.0226%, sas) (gnomAD).

What do computational predictors say about AASS p.Arg471Cys (c.1411C>T)?

AlphaMissense predicts likely benign (score 0.1147) — an in-silico prediction, not a clinical call.

AASS p.Arg471Cys

c.1411C>T · VCV3265007

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1147 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0226%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1147	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -9.23	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.8	GERP -1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 57 kb · p 0.0048 · regional, not allelic
Overall
CADD	20.4	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 0.0226% South Asian · 17/75,132 alleles

Filtering AF 0.0143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.00375% 48/1,279,322 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0226%	4,420
African / African-American	0.0219%	4,561
Admixed American	0.0159%	6,296
East Asian	0.00562%	17,807
Remaining individualsnot grpmax-eligible	0.00417%	23,977
European (non-Finnish)	0.000845%	118,371

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.Arg471Cys
Coding: c.1411C>T
MANE Select: NM_005763
Type: single nucleotide variant
Location: chr7:122098862 (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 471: the 'lysine-ketoglutarate reductase' 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.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
AASS p.Ser664Pro 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-arg471cys (accessed [today's date]).

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