Is CD276 p.Arg113His (c.338G>A) pathogenic?

CD276 p.Arg113His (c.338G>A) is classified Likely benign in CD276 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.0947); Very rare (popmax 0.00668%, eas); Associated with long QT syndrome.

What condition is associated with CD276 p.Arg113His (c.338G>A)?

CD276 p.Arg113His (c.338G>A) is associated with long QT syndrome (ClinVar).

How common is CD276 p.Arg113His (c.338G>A) in the general population?

CD276 p.Arg113His (c.338G>A) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about CD276 p.Arg113His (c.338G>A)?

AlphaMissense predicts likely benign (score 0.0947) — an in-silico prediction, not a clinical call.

CD276 p.Arg113His

c.338G>A · rs770650860 · VCV207869

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0947 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

long QT syndrome

Computational evidence

Protein change
AlphaMissense	0.0947	likely benign
REVEL	0.351	indeterminate
SaProt	LLR -11.65	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 1.4, phastCons 0.99
Regional constraint	o/e 0.88	unconstrained · MANE · 13 kb · p 0.0018 · regional, not allelic
Overall
CADD	26.3	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 0.00668% East Asian · 3/44,880 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00347% 56/1,612,878 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,960
South Asian	0.00659%	15,179
European (non-Finnish)	0.00364%	27,441
Admixed American	0.00333%	29,995
Remaining individualsnot grpmax-eligible	0.0016%	62,480
African / African-American	0.00133%	74,930

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: CD276
Protein: p.Arg113His
Coding: c.338G>A
MANE Select: NM_001024736
dbSNP: rs770650860
Type: single nucleotide variant
Location: chr15:73702513 (GRCh38)
Gene constraint: LOEUF 0.888 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.63 · 3 PDB
Residue 113: a disulfide bond; the ig-like v-type 1 domain

Full CD276 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

long QT syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD276 p.Arg113Gly Uncertain significance ★ ⚠ same residue
CD276 p.Leu419= Benign ★★ same type
CD276 p.Ala132Ser Uncertain significance ★ ⚠ same type
CD276 p.Ala139Ser Uncertain significance ★ ⚠ same type
CD276 p.Ala28Ser Uncertain significance ★ ⚠ same type
CD276 p.Ala312Thr Uncertain significance ★ ⚠ same type
CD276 p.Ala350Thr Uncertain significance ★ ⚠ same type
CD276 p.Ala351Val 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/cd276-p-arg113his (accessed [today's date]).

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