Is ERC1 p.Ala940= (c.2820C>T) pathogenic?

ERC1 p.Ala940= (c.2820C>T) is classified Benign in ERC1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-23). Common (popmax 6.62%, mid) — too common for a highly-penetrant pathogenic allele; Associated with ERC1-related disorder.

What condition is associated with ERC1 p.Ala940= (c.2820C>T)?

ERC1 p.Ala940= (c.2820C>T) is associated with ERC1-related disorder (ClinVar).

ERC1 p.Ala940=

Q: How common is ERC1 p.Ala940= (c.2820C>T) in the general population?

ERC1 p.Ala940= (c.2820C>T) is common (popmax 6.62%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2820C>T · rs35478691 · VCV3057218

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 6.62%, mid) — too common for a highly-penetrant pathogenic allele

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 1.8	GERP 0.4, phastCons 1
Overall
CADD	12.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.62% Middle Eastern · 396/5,978 alleles

Filtering AF 6.09% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.87%

Overall 3.15% 50,899/1,613,850 alleles · common exomes 46,226/1,461,566 · genomes 4,673/152,284 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	6.62%	15
Ashkenazi Jewishnot grpmax-eligible	5.32%	19
South Asian	4.35%	23
African / African-American	3.36%	30
Remaining individualsnot grpmax-eligible	3.17%	32
European (non-Finnish)	3.13%	32
Finnishnot grpmax-eligible	2.64%	38
Admixed American	2.16%	46
East Asian	1.16%	86
Amishnot grpmax-eligible	0.877%	114

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.Ala940=
Coding: c.2820C>T
MANE Select: NM_178040
dbSNP: rs35478691
Type: single nucleotide variant
Location: chr12:1371872 (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 p.Ala940Ser Uncertain significance ★ ⚠ same residue
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.Arg103Pro Likely benign ⚠ same condition
ERC1 p.Gln16His Benign same condition
ERC1 p.His342= Likely 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-ala940 (accessed [today's date]).

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