Is ECI2 p.Met47Val (c.139A>G) pathogenic?

ECI2 p.Met47Val (c.139A>G) is classified Likely benign in ECI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-05). AlphaMissense: likely benign (0.0528); Ultra-rare (popmax 0.028%, afr).

How common is ECI2 p.Met47Val (c.139A>G) in the general population?

ECI2 p.Met47Val (c.139A>G) is ultra-rare (popmax 0.028%, afr) (gnomAD).

What do computational predictors say about ECI2 p.Met47Val (c.139A>G)?

AlphaMissense predicts likely benign (score 0.0528) — an in-silico prediction, not a clinical call.

ECI2 p.Met47Val

c.139A>G · rs142020884 · VCV3086963

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0528 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.028%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0528	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -2.79	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 -7.8	GERP -4.1
Regional constraint	o/e 0.99	unconstrained · MANE · 20 kb · p 0.84 · regional, not allelic
Overall
CADD	0.006	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 0.028% African / African-American · 21/75,052 alleles

Filtering AF 0.0187% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0157%

Overall 0.00266% 43/1,614,084 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.028%	3,574
Remaining individualsnot grpmax-eligible	0.0048%	20,832
East Asian	0.00446%	22,438
European (non-Finnish)	0.00136%	73,749
South Asian	0.0011%	91,066

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: ECI2
Protein: p.Met47Val
Coding: c.139A>G
MANE Select: NM_206836
dbSNP: rs142020884
Type: single nucleotide variant
Location: chr6:4133623 (GRCh38)
Gene constraint: LOEUF 0.949 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.40 · 5 PDB
Residue 47: the acb domain; a UniProt-annotated variant site (in); an α-helix

Full ECI2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ECI2 p.Ala11Pro Uncertain significance ★ ⚠ same type
ECI2 p.Ala67Thr Uncertain significance ★ ⚠ same type
ECI2 p.Ala67Val Uncertain significance ★ ⚠ same type
ECI2 p.Ala7Val Uncertain significance ★ ⚠ same type
ECI2 p.Ala95Thr Uncertain significance ★ ⚠ same type
ECI2 p.Arg157Trp Uncertain significance ★ ⚠ same type
ECI2 p.Cys15Tyr Uncertain significance ★ ⚠ same type
ECI2 p.Glu147Lys Uncertain significance ★ ⚠ same type

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/eci2-p-met47val (accessed [today's date]).

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