Is ABLIM3 p.Arg25Cys (c.73C>T) pathogenic?

ABLIM3 p.Arg25Cys (c.73C>T) is classified Uncertain significance in ABLIM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely pathogenic (0.6265); Ultra-rare (popmax 0.0166%, mid).

How common is ABLIM3 p.Arg25Cys (c.73C>T) in the general population?

ABLIM3 p.Arg25Cys (c.73C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about ABLIM3 p.Arg25Cys (c.73C>T)?

AlphaMissense predicts likely pathogenic (score 0.6265) — an in-silico prediction, not a clinical call.

ABLIM3 p.Arg25Cys

c.73C>T · VCV4178551

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6265 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6265	likely pathogenic
REVEL	0.751	pathogenic-leaning
SaProt	LLR -13.67	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.55, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 116 kb · p 0.0017 · regional, not allelic
Overall
CADD	28.5	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 0.0166% Middle Eastern · 1/6,036 alleles

Filtering AF 0.00626% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00582%

Overall 0.006% 96/1,599,394 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,036
European (non-Finnish)	0.00758%	13,185
African / African-American	0.0027%	36,970
South Asian	0.00225%	44,435
Remaining individualsnot grpmax-eligible	0.00162%	61,896
Finnishnot grpmax-eligible	0.00156%	63,902

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: ABLIM3
Protein: p.Arg25Cys
Coding: c.73C>T
MANE Select: NM_014945
Type: single nucleotide variant
Location: chr5:149183511 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.31 · 2 PDB
Residue 25: the lim zinc-binding 1 domain

Full ABLIM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABLIM3 p.Arg513Cys Uncertain significance ★★ ⚠ same type
ABLIM3 p.Ala166Gly Uncertain significance ★ ⚠ same type
ABLIM3 p.Ala297Val Uncertain significance ★ ⚠ same type
ABLIM3 p.Ala371Asp Uncertain significance ★ ⚠ same type
ABLIM3 p.Ala600Pro Uncertain significance ★ ⚠ same type
ABLIM3 p.Arg15Trp Uncertain significance ★ ⚠ same type
ABLIM3 p.Arg215Gln Uncertain significance ★ ⚠ same type
ABLIM3 p.Arg238Cys 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/ablim3-p-arg25cys (accessed [today's date]).

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