Is ABT1 p.Arg120Pro (c.359G>C) pathogenic?

ABT1 p.Arg120Pro (c.359G>C) is classified Uncertain significance in ABT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-05). AlphaMissense: likely pathogenic (0.9383); Very rare (popmax 0.0011%, sas).

How common is ABT1 p.Arg120Pro (c.359G>C) in the general population?

ABT1 p.Arg120Pro (c.359G>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ABT1 p.Arg120Pro (c.359G>C)?

AlphaMissense predicts likely pathogenic (score 0.9383) — an in-silico prediction, not a clinical call.

ABT1 p.Arg120Pro

c.359G>C · rs782010945 · VCV3132700

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9383 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9383	likely pathogenic · top 9% in ABT1
REVEL	0.302	indeterminate
SaProt	LLR -16.74	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 0.59, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 1,659 bp · p 0.01 · regional, not allelic
Overall
CADD	26.0	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 0.0011% South Asian · 1/91,090 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,880 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,090
European (non-Finnish)	0.000169%	590,023

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: ABT1
Protein: p.Arg120Pro
Coding: c.359G>C
MANE Select: NM_013375
dbSNP: rs782010945
Type: single nucleotide variant
Location: chr6:26598031 (GRCh38)
Gene constraint: LOEUF 1.2 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.08
Residue 120: the rrm domain

Full ABT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABT1 p.Arg120His Uncertain significance ★ ⚠ same residue
ABT1 p.Ala122Val Uncertain significance ★ ⚠ same type
ABT1 p.Ala234Thr Uncertain significance ★ ⚠ same type
ABT1 p.Ala25Val Uncertain significance ★ ⚠ same type
ABT1 p.Ala3Val Uncertain significance ★ ⚠ same type
ABT1 p.Ala68Val Uncertain significance ★ ⚠ same type
ABT1 p.Ala92Val Uncertain significance ★ ⚠ same type
ABT1 p.Ala93Val 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/abt1-p-arg120pro (accessed [today's date]).

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