Is IBA57 p.Ala26Val (c.77C>T) pathogenic?

IBA57 p.Ala26Val (c.77C>T) is classified Uncertain significance in IBA57 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-01). AlphaMissense: likely benign (0.0822); Ultra-rare (popmax 0.012%, afr); Associated with Inborn genetic diseases.

What condition is associated with IBA57 p.Ala26Val (c.77C>T)?

IBA57 p.Ala26Val (c.77C>T) is associated with Inborn genetic diseases (ClinVar).

How common is IBA57 p.Ala26Val (c.77C>T) in the general population?

IBA57 p.Ala26Val (c.77C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about IBA57 p.Ala26Val (c.77C>T)?

AlphaMissense predicts likely benign (score 0.0822) — an in-silico prediction, not a clinical call.

IBA57 p.Ala26Val

c.77C>T · VCV3527344

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0822 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0822	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -6.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.8
Regional constraint	o/e 1.22	unconstrained · MANE · 9,693 bp · p 1.1e-06 · regional, not allelic
Overall
CADD	0.375	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.012% African / African-American · 8/66,540 alleles

Filtering AF 0.00595% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00432%

Overall 0.000785% 11/1,400,606 alleles · ultra-rare exomes 4/1,248,454 · genomes 7/152,152 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,318
Admixed American	0.00616%	16,232
Remaining individualsnot grpmax-eligible	0.00187%	53,420

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: IBA57
Protein: p.Ala26Val
Coding: c.77C>T
MANE Select: NM_001010867
Type: single nucleotide variant
Location: chr1:228165893 (GRCh38)
Gene constraint: LOEUF 1.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.07 · 3 PDB

Full IBA57 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IBA57 p.Ala26= Likely benign ★ same residue
IBA57 p.Ala345Thr Uncertain significance ★★ ⚠ same condition
IBA57 p.Ala91Gly Uncertain significance ★★ ⚠ same condition
IBA57 p.Arg28Gly Uncertain significance ★★ ⚠ same condition
IBA57 p.Gly195Ala Uncertain significance ★★ ⚠ same condition
IBA57 p.Ile327Phe Uncertain significance ★★ ⚠ same condition
IBA57 p.Pro236Ala Uncertain significance ★★ ⚠ same condition
IBA57 p.Ser82Thr Uncertain significance ★★ ⚠ same condition

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/iba57-p-ala26val (accessed [today's date]).

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