Is ABLIM2 p.Pro295Leu (c.884C>T) pathogenic?

ABLIM2 p.Pro295Leu (c.884C>T) is classified Uncertain significance in ABLIM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-17). AlphaMissense: likely pathogenic (0.6648); Very rare (popmax 0.00941%, nfe).

How common is ABLIM2 p.Pro295Leu (c.884C>T) in the general population?

ABLIM2 p.Pro295Leu (c.884C>T) is very rare (popmax 0.00941%, nfe) (gnomAD).

What do computational predictors say about ABLIM2 p.Pro295Leu (c.884C>T)?

AlphaMissense predicts likely pathogenic (score 0.6648) — an in-silico prediction, not a clinical call.

ABLIM2 p.Pro295Leu

c.884C>T · rs757458512 · VCV2511158

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6648 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00941%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6648	likely pathogenic
REVEL	0.502	indeterminate
SaProt	LLR -9.13	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 192 kb · p 0.27 · 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 0.00941% European (non-Finnish) · 111/1,179,798 alleles

Filtering AF 0.00791% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00744%

Overall 0.00744% 120/1,613,746 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00941%	10,629
Admixed American	0.00667%	14,999
Remaining individualsnot grpmax-eligible	0.0048%	20,820
Finnishnot grpmax-eligible	0.00156%	64,010
African / African-American	0.00133%	74,910

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: ABLIM2
Protein: p.Pro295Leu
Coding: c.884C>T
MANE Select: NM_001130083
dbSNP: rs757458512
Type: single nucleotide variant
Location: chr4:8045180 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.21 · 3 PDB
Residue 295: the 'disordered' region

Full ABLIM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABLIM2 c.763+4C>T Benign ★★ same type
ABLIM2 c.763+5A>G Benign ★★ same type
ABLIM2 p.Ala144Thr Uncertain significance ★ ⚠ same type
ABLIM2 p.Ala21Val Uncertain significance ★ ⚠ same type
ABLIM2 p.Ala288Val Uncertain significance ★ ⚠ same type
ABLIM2 p.Ala476Ser Uncertain significance ★ ⚠ same type
ABLIM2 p.Ala565Asp Uncertain significance ★ ⚠ same type
ABLIM2 p.Ala97Val 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/ablim2-p-pro295leu (accessed [today's date]).

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