Is ERC1 p.His342= (c.1026C>T) pathogenic?

ERC1 p.His342= (c.1026C>T) is classified Likely benign in ERC1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-25). Rare (popmax 0.105%, amr); Associated with ERC1-related disorder.

What condition is associated with ERC1 p.His342= (c.1026C>T)?

ERC1 p.His342= (c.1026C>T) is associated with ERC1-related disorder (ClinVar).

How common is ERC1 p.His342= (c.1026C>T) in the general population?

ERC1 p.His342= (c.1026C>T) is rare (popmax 0.105%, amr) (gnomAD).

ERC1 p.His342=

c.1026C>T · rs187560506 · VCV3047384

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.105%, amr)

Conditions

ERC1-related disorder

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 -20	GERP -5.5
Overall
CADD	0.286	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.105% Admixed American · 63/59,818 alleles

Filtering AF 0.0844% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0769%

Overall 0.00744% 120/1,613,362 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.105%	949
Remaining individualsnot grpmax-eligible	0.0304%	3,287
African / African-American	0.00667%	14,985
European (non-Finnish)	0.00263%	38,058
Finnishnot grpmax-eligible	0.00156%	64,004
South Asian	0.0011%	90,938

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: ERC1
Protein: p.His342=
Coding: c.1026C>T
MANE Select: NM_178040
dbSNP: rs187560506
Type: single nucleotide variant
Location: chr12:1083520 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.79 (gnomAD)
Structure: AlphaFold pLDDT 75.64

Full ERC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ERC1-related disorder

Similar variants

ERC1 c.1738-6A>C Likely benign same condition
ERC1 c.2158-4G>A Benign same condition
ERC1 c.3214-9201G>T Likely benign same condition
ERC1 c.3214-9246C>T Benign same condition
ERC1 p.Ala940= Benign same condition
ERC1 p.Arg103Pro Likely benign ⚠ same condition
ERC1 p.Gln16His Benign same condition
ERC1 p.Ile629Val Benign ⚠ same condition

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/erc1-p-his342 (accessed [today's date]).

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