Is ERBB2 p.Asp502= (c.1506C>T) pathogenic?

ERBB2 p.Asp502= (c.1506C>T) is classified Likely benign in ERBB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-06). Ultra-rare (popmax 0.0164%, mid).

How common is ERBB2 p.Asp502= (c.1506C>T) in the general population?

ERBB2 p.Asp502= (c.1506C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

ERBB2 p.Asp502=

c.1506C>T · rs752759368 · VCV2170355

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -5.3
Overall
CADD	0.788	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.00311% 50/1,609,032 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
African / African-American	0.0133%	7,494
Remaining individualsnot grpmax-eligible	0.0112%	8,923
Admixed American	0.01%	9,997
European (non-Finnish)	0.00212%	47,197
South Asian	0.0011%	91,054

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: ERBB2
Protein: p.Asp502=
Coding: c.1506C>T
MANE Select: NM_004448
dbSNP: rs752759368
Type: single nucleotide variant
Location: chr17:39715932 (GRCh38)
Gene constraint: LOEUF 0.518 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 74.65 · 63 PDB
Residue 502: an α-helix; a disulfide bond

Full ERBB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERBB2 p.Asp502Glu Uncertain significance ★ ⚠ same residue
ERBB2 p.Ala598Asp Uncertain significance ★★ ⚠ same type
ERBB2 p.Ala644Thr Uncertain significance ★★ ⚠ same type
ERBB2 p.Arg1048Cys Uncertain significance ★★ ⚠ same type
ERBB2 p.Arg188Cys Uncertain significance ★★ ⚠ same type
ERBB2 p.Arg188His Uncertain significance ★★ ⚠ same type
ERBB2 p.Arg190Gln Uncertain significance ★★ ⚠ same type
ERBB2 p.Arg203His 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/erbb2-p-asp502 (accessed [today's date]).

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