Is ABAT p.Arg473Cys (c.1417C>T) pathogenic?

ABAT p.Arg473Cys (c.1417C>T) is classified Uncertain significance in ABAT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-30). AlphaMissense: likely pathogenic (0.9527); Very rare (popmax 0.000254%, nfe).

How common is ABAT p.Arg473Cys (c.1417C>T) in the general population?

ABAT p.Arg473Cys (c.1417C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about ABAT p.Arg473Cys (c.1417C>T)?

AlphaMissense predicts likely pathogenic (score 0.9527) — an in-silico prediction, not a clinical call.

ABAT p.Arg473Cys

c.1417C>T · rs748530728 · VCV2579783

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9527 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9527	likely pathogenic
REVEL	0.93	moderately pathogenic-leaning
SaProt	LLR -15.52	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.24	loss · gain 0.04 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 46 kb · p 0.32 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,034 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,614,038 alleles · very rare

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: ABAT
Protein: p.Arg473Cys
Coding: c.1417C>T
MANE Select: NM_020686
dbSNP: rs748530728
Type: single nucleotide variant
Location: chr16:8781344 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.91

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

Similar variants

ABAT p.Arg473His Uncertain significance ★ ⚠ same residue
ABAT c.168+1G>A Pathogenic ★★ same type
ABAT p.Arg92Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
ABAT p.Gln8Ter Pathogenic/Likely pathogenic ★★ same type
ABAT p.Leu211Phe Pathogenic/Likely pathogenic ★★ same type
ABAT p.Tyr376Ter Pathogenic/Likely pathogenic ★★ same type
ABAT c.1381+6G>T Uncertain significance ★★ same type
ABAT p.Ala162Thr 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/abat-p-arg473cys (accessed [today's date]).

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