Is ABR p.Pro58Leu (c.173C>T) pathogenic?

ABR p.Pro58Leu (c.173C>T) is classified Uncertain significance in ABR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely pathogenic (0.941); Very rare (popmax 0.00223%, eas).

How common is ABR p.Pro58Leu (c.173C>T) in the general population?

ABR p.Pro58Leu (c.173C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ABR p.Pro58Leu (c.173C>T)?

AlphaMissense predicts likely pathogenic (score 0.941) — an in-silico prediction, not a clinical call.

ABR p.Pro58Leu

c.173C>T · VCV4636443

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.941 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.941	likely pathogenic
REVEL	0.288	benign-leaning
SaProt	LLR -9.04	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 79 kb · p 0.71 · regional, not allelic
Overall
CADD	33.0	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 0.00223% East Asian · 1/44,822 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000685% 10/1,460,854 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,822
Remaining individualsnot grpmax-eligible	0.0016%	62,454
African / African-American	0.00133%	75,000
South Asian	0.0011%	91,010
European (non-Finnish)	0.000509%	196,595

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: ABR
Protein: p.Pro58Leu
Coding: c.173C>T
MANE Select: NM_021962
Type: single nucleotide variant
Location: chr17:1125256 (GRCh38)
Gene constraint: LOEUF 0.431 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 79.10
Residue 58: the 'disordered' region

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

Similar variants

ABR c.2490+4C>T Benign ★★ same type
ABR p.Ala31Glu Benign ★★ same type
ABR p.Arg124Gln Benign ★★ same type
ABR p.Glu73Asp Benign ★★ same type
ABR p.Gly114Glu Benign ★★ same type
ABR p.Gly66= Benign ★★ same type
ABR p.Ala62Thr Uncertain significance ★ ⚠ same type
ABR p.Ala688Thr 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/abr-p-pro58leu (accessed [today's date]).

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