Is CIB2 p.Val54Met (c.160G>A) pathogenic?

CIB2 p.Val54Met (c.160G>A) is classified Uncertain significance in CIB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-07). AlphaMissense: likely pathogenic (0.6878); Very rare (popmax 0.008%, afr).

How common is CIB2 p.Val54Met (c.160G>A) in the general population?

CIB2 p.Val54Met (c.160G>A) is very rare (popmax 0.008%, afr) (gnomAD).

What do computational predictors say about CIB2 p.Val54Met (c.160G>A)?

AlphaMissense predicts likely pathogenic (score 0.6878) — an in-silico prediction, not a clinical call.

CIB2 p.Val54Met

c.160G>A · rs201062535 · VCV1041997

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6878 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.008%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6878	likely pathogenic
REVEL	0.412	indeterminate
SaProt	LLR -10.08	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 7.2	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 26 kb · p 0.17 · regional, not allelic
Overall
CADD	27.1	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 0.008% African / African-American · 6/75,020 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.00105% 17/1,614,146 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.008%	12,503
Remaining individualsnot grpmax-eligible	0.0032%	31,254
East Asian	0.00223%	44,882
Admixed American	0.00167%	60,016
South Asian	0.0011%	91,088
European (non-Finnish)	0.000508%	196,671

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: CIB2
Protein: p.Val54Met
Coding: c.160G>A
MANE Select: NM_006383
dbSNP: rs201062535
Type: single nucleotide variant
Location: chr15:78111203 (GRCh38)
Gene constraint: LOEUF 1.274 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.71 · 1 PDB
Residue 54: a UniProt-annotated variant site (in dfnb48)

Full CIB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIB2 p.Arg104Ter Pathogenic/Likely pathogenic ★★ same type
CIB2 p.Arg33Ter Pathogenic ★★ same type
CIB2 p.Arg66Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
CIB2 c.198+3A>G Uncertain significance ★★ same type
CIB2 p.Ala108Thr Uncertain significance ★★ ⚠ same type
CIB2 p.Ala76Val Uncertain significance ★★ ⚠ same type
CIB2 p.Arg134Gln Uncertain significance ★★ ⚠ same type
CIB2 p.Arg134Trp 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/cib2-p-val54met (accessed [today's date]).

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