Is ABLIM2 p.Phe116Val (c.346T>G) pathogenic?

ABLIM2 p.Phe116Val (c.346T>G) is classified Uncertain significance in ABLIM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely pathogenic (0.9903); Very rare (popmax 0.00204%, nfe).

How common is ABLIM2 p.Phe116Val (c.346T>G) in the general population?

ABLIM2 p.Phe116Val (c.346T>G) is very rare (popmax 0.00204%, nfe) (gnomAD).

What do computational predictors say about ABLIM2 p.Phe116Val (c.346T>G)?

AlphaMissense predicts likely pathogenic (score 0.9903) — an in-silico prediction, not a clinical call.

ABLIM2 p.Phe116Val

c.346T>G · VCV4636413

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9903 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00204%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9903	likely pathogenic · top 8% in ABLIM2
REVEL	0.907	moderately pathogenic-leaning
SaProt	LLR -13.43	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 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 192 kb · p 0.27 · regional, not allelic
Overall
CADD	28.1	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 0.00204% European (non-Finnish) · 24/1,178,750 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00161% 26/1,611,262 alleles · very rare exomes 25/1,459,544 · genomes 1/151,718 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00204%	49,114
Remaining individualsnot grpmax-eligible	0.0016%	62,334
African / African-American	0.00134%	74,680

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.Phe116Val
Coding: c.346T>G
MANE Select: NM_001130083
Type: single nucleotide variant
Location: chr4:8088277 (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.Phe116Leu 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-phe116val (accessed [today's date]).

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