Is ERBB2 p.Glu79Ala (c.236A>C) pathogenic?

ERBB2 p.Glu79Ala (c.236A>C) is classified Likely benign in ERBB2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-21). AlphaMissense: likely pathogenic (0.9075); Low-frequency (popmax 1.02%, afr).

How common is ERBB2 p.Glu79Ala (c.236A>C) in the general population?

ERBB2 p.Glu79Ala (c.236A>C) is low-frequency (popmax 1.02%, afr) (gnomAD).

What do computational predictors say about ERBB2 p.Glu79Ala (c.236A>C)?

AlphaMissense predicts likely pathogenic (score 0.9075) — an in-silico prediction, not a clinical call.

ERBB2 p.Glu79Ala

c.236A>C · rs61737968 · VCV134087

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9075 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.02%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9075	likely pathogenic
REVEL	0.955	strongly pathogenic-leaning
SaProt	LLR -15.78	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 16 kb · p 1.3e-16 · regional, not allelic
Overall
CADD	28.1	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 1.02% African / African-American · 769/75,028 alleles

Filtering AF 0.965% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.941%

Overall 0.0562% 907/1,613,058 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.02%	98
Admixed American	0.105%	952
Remaining individualsnot grpmax-eligible	0.088%	1,136
Middle Eastern	0.033%	3,028
South Asian	0.0022%	45,529
European (non-Finnish)	0.00136%	73,695

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.Glu79Ala
Coding: c.236A>C
MANE Select: NM_004448
dbSNP: rs61737968
Type: single nucleotide variant
Location: chr17:39708331 (GRCh38)
Gene constraint: LOEUF 0.518 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 74.65 · 63 PDB
Residue 79: a β-strand

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

Similar variants

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
ERBB2 p.Arg217Cys 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-glu79ala (accessed [today's date]).

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