Is CBLC p.Arg330His (c.989G>A) pathogenic?

CBLC p.Arg330His (c.989G>A) is classified Likely benign in CBLC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely benign (0.0636); Ultra-rare (popmax 0.0201%, eas).

How common is CBLC p.Arg330His (c.989G>A) in the general population?

CBLC p.Arg330His (c.989G>A) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

What do computational predictors say about CBLC p.Arg330His (c.989G>A)?

AlphaMissense predicts likely benign (score 0.0636) — an in-silico prediction, not a clinical call.

CBLC p.Arg330His

c.989G>A · rs139273613 · VCV3137985

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0636 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0636	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -3.92	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 -0.44	GERP -4.9
Regional constraint	o/e 1.00	unconstrained · MANE · 19 kb · p 0.99 · regional, not allelic
Overall
CADD	4.444	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 0.0201% East Asian · 9/44,858 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00192% 31/1,613,418 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,984
Middle Eastern	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.0064%	15,617
South Asian	0.00549%	18,213
Finnishnot grpmax-eligible	0.00313%	31,995
European (non-Finnish)	0.000848%	117,971

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: CBLC
Protein: p.Arg330His
Coding: c.989G>A
MANE Select: NM_012116
dbSNP: rs139273613
Type: single nucleotide variant
Location: chr19:44790075 (GRCh38)
Gene constraint: LOEUF 1.058 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.85 · 7 PDB
Residue 330: the 'linker' region

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

Similar variants

CBLC p.Arg330Cys Uncertain significance ★ ⚠ same residue
CBLC p.Ala122Ser Uncertain significance ★ ⚠ same type
CBLC p.Ala137Val Uncertain significance ★ ⚠ same type
CBLC p.Ala21Val Uncertain significance ★ ⚠ same type
CBLC p.Ala377Pro Uncertain significance ★ ⚠ same type
CBLC p.Ala398Val Uncertain significance ★ ⚠ same type
CBLC p.Ala433Ser Uncertain significance ★ ⚠ same type
CBLC p.Ala450Gly 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/cblc-p-arg330his (accessed [today's date]).

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