Is ERC1 p.Ser50Gly (c.148A>G) pathogenic?

ERC1 p.Ser50Gly (c.148A>G) is classified Benign in ERC1 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2019-05-28). AlphaMissense: likely benign (0.0556); Common (popmax 6.81%, mid) — too common for a highly-penetrant pathogenic allele; Associated with ERC1-related disorder.

What condition is associated with ERC1 p.Ser50Gly (c.148A>G)?

ERC1 p.Ser50Gly (c.148A>G) is associated with ERC1-related disorder (ClinVar).

What do computational predictors say about ERC1 p.Ser50Gly (c.148A>G)?

AlphaMissense predicts likely benign (score 0.0556) — an in-silico prediction, not a clinical call.

ERC1 p.Ser50Gly

Q: How common is ERC1 p.Ser50Gly (c.148A>G) in the general population?

ERC1 p.Ser50Gly (c.148A>G) is common (popmax 6.81%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.148A>G · rs35037408 · VCV3037380

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0556 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.81%, mid) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ERC1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0556	likely benign
REVEL	0.28	benign-leaning
SaProt	LLR -5.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -1.1, phastCons 0.95
Regional constraint	o/e 0.89	unconstrained · MANE · 462 kb · p 5.7e-05 · regional, not allelic
Overall
CADD	16.47	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 6.81% Middle Eastern · 413/6,062 alleles

Filtering AF 6.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.06%

Overall 3.39% 54,664/1,614,182 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	6.81%	15
Ashkenazi Jewishnot grpmax-eligible	6.64%	15
Amishnot grpmax-eligible	4.28%	23
European (non-Finnish)	3.88%	26
Remaining individualsnot grpmax-eligible	3.53%	28
Admixed American	2.74%	37
South Asian	1.68%	60
Finnishnot grpmax-eligible	0.954%	105
African / African-American	0.624%	160
East Asian	0.00446%	22,444

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.Ser50Gly
Coding: c.148A>G
MANE Select: NM_178040
dbSNP: rs35037408
Type: single nucleotide variant
Location: chr12:1028051 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.79 (gnomAD)
Structure: AlphaFold pLDDT 75.64
Residue 50: the 'disordered' region; a UniProt-annotated variant site (in)

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.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-ser50gly (accessed [today's date]).

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