Is ABLIM3 p.Ser583Pro (c.1747T>C) pathogenic?

ABLIM3 p.Ser583Pro (c.1747T>C) is classified Uncertain significance in ABLIM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: likely pathogenic (0.7795); Ultra-rare (popmax 0.0147%, afr).

How common is ABLIM3 p.Ser583Pro (c.1747T>C) in the general population?

ABLIM3 p.Ser583Pro (c.1747T>C) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

What do computational predictors say about ABLIM3 p.Ser583Pro (c.1747T>C)?

AlphaMissense predicts likely pathogenic (score 0.7795) — an in-silico prediction, not a clinical call.

ABLIM3 p.Ser583Pro

c.1747T>C · VCV3994081

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7795 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7795	likely pathogenic
REVEL	0.271	benign-leaning
SaProt	LLR -10.16	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, 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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% African / African-American · 11/74,938 alleles

Filtering AF 0.00815% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.000743% 12/1,614,064 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,813
European (non-Finnish)	8.47e-05%	1,180,026

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.Ser583Pro
Coding: c.1747T>C
MANE Select: NM_014945
Type: single nucleotide variant
Location: chr5:149250464 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.31 · 2 PDB

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-ser583pro (accessed [today's date]).

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