Is ERC1 p.Ile629Val (c.1885A>G) pathogenic?

ERC1 p.Ile629Val (c.1885A>G) is classified Benign in ERC1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-21). AlphaMissense: likely benign (0.2099); Low-frequency (popmax 1.63%, afr); Associated with ERC1-related disorder.

What condition is associated with ERC1 p.Ile629Val (c.1885A>G)?

ERC1 p.Ile629Val (c.1885A>G) is associated with ERC1-related disorder (ClinVar).

How common is ERC1 p.Ile629Val (c.1885A>G) in the general population?

ERC1 p.Ile629Val (c.1885A>G) is low-frequency (popmax 1.63%, afr) (gnomAD).

What do computational predictors say about ERC1 p.Ile629Val (c.1885A>G)?

AlphaMissense predicts likely benign (score 0.2099) — an in-silico prediction, not a clinical call.

ERC1 p.Ile629Val

c.1885A>G · rs141757454 · VCV3053450

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2099 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.63%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ERC1-related disorder

Computational evidence

Protein change
AlphaMissense	0.2099	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -7.86	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 11	GERP 2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 462 kb · p 5.7e-05 · regional, not allelic
Overall
CADD	24.9	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 1.63% African / African-American · 1,222/75,018 alleles

Filtering AF 1.55% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.52%

Overall 0.0818% 1,320/1,613,592 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.63%	61
Remaining individualsnot grpmax-eligible	0.0704%	1,420
Admixed American	0.0667%	1,499
Middle Eastern	0.033%	3,031
South Asian	0.0044%	22,750
European (non-Finnish)	0.000678%	147,462

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.Ile629Val
Coding: c.1885A>G
MANE Select: NM_178040
dbSNP: rs141757454
Type: single nucleotide variant
Location: chr12:1181934 (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.Ile629Thr 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.Arg103Pro Likely 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-ile629val (accessed [today's date]).

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