Is ERC1 p.Arg103Pro (c.308G>C) pathogenic?

ERC1 p.Arg103Pro (c.308G>C) is classified Likely benign in ERC1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-12-28). AlphaMissense: likely pathogenic (0.9299); Rare (popmax 0.176%, sas); Associated with ERC1-related disorder.

What condition is associated with ERC1 p.Arg103Pro (c.308G>C)?

ERC1 p.Arg103Pro (c.308G>C) is associated with ERC1-related disorder (ClinVar).

How common is ERC1 p.Arg103Pro (c.308G>C) in the general population?

ERC1 p.Arg103Pro (c.308G>C) is rare (popmax 0.176%, sas) (gnomAD).

What do computational predictors say about ERC1 p.Arg103Pro (c.308G>C)?

AlphaMissense predicts likely pathogenic (score 0.9299) — an in-silico prediction, not a clinical call.

ERC1 p.Arg103Pro

c.308G>C · rs535851221 · VCV3054082

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9299 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.176%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ERC1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9299	likely pathogenic
REVEL	0.779	moderately pathogenic-leaning
SaProt	LLR -6.92	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 462 kb · p 5.7e-05 · regional, not allelic
Overall
CADD	31.0	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 0.176% South Asian · 160/91,068 alleles

Filtering AF 0.153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.145%

Overall 0.0107% 173/1,614,130 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.176%	569
Remaining individualsnot grpmax-eligible	0.0176%	5,683
African / African-American	0.00133%	75,028
European (non-Finnish)	8.47e-05%	1,180,034

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.Arg103Pro
Coding: c.308G>C
MANE Select: NM_178040
dbSNP: rs535851221
Type: single nucleotide variant
Location: chr12:1028211 (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.Arg103Gln Uncertain significance ★ ⚠ same residue
ERC1 p.Arg103Trp 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.Ala940= Benign same condition
ERC1 p.Gln16His 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-arg103pro (accessed [today's date]).

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