Is ABLIM2 p.Phe116Leu (c.348C>A) pathogenic?

ABLIM2 p.Phe116Leu (c.348C>A) is classified Uncertain significance in ABLIM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely pathogenic (0.9982); Very rare (popmax 0.00223%, eas).

How common is ABLIM2 p.Phe116Leu (c.348C>A) in the general population?

ABLIM2 p.Phe116Leu (c.348C>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ABLIM2 p.Phe116Leu (c.348C>A)?

AlphaMissense predicts likely pathogenic (score 0.9982) — an in-silico prediction, not a clinical call.

ABLIM2 p.Phe116Leu

c.348C>A · rs747138981 · VCV3132146

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9982 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9982	likely pathogenic · top 1% in ABLIM2
REVEL	0.552	indeterminate
SaProt	LLR -13.70	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 0.26	GERP -3.9, phastCons 0.86
Regional constraint	o/e 0.96	unconstrained · MANE · 192 kb · p 0.27 · regional, not allelic
Overall
CADD	20.7	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 0.00223% East Asian · 1/44,792 alleles

Overall 0.000137% 2/1,460,320 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,792
European (non-Finnish)	8.48e-05%	1,179,226

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.Phe116Leu
Coding: c.348C>A
MANE Select: NM_001130083
dbSNP: rs747138981
Type: single nucleotide variant
Location: chr4:8088275 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.21 · 3 PDB
Residue 116: the lim zinc-binding 2 domain; an α-helix

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

Similar variants

ABLIM2 p.Phe116Val Uncertain significance ★ ⚠ same residue
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

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-phe116leu (accessed [today's date]).

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