Is EMC1 p.Arg706Trp (c.2116C>T) pathogenic?

EMC1 p.Arg706Trp (c.2116C>T) is classified Uncertain significance in EMC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-13). AlphaMissense: likely benign (0.162); Very rare (popmax 0.00223%, eas).

How common is EMC1 p.Arg706Trp (c.2116C>T) in the general population?

EMC1 p.Arg706Trp (c.2116C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about EMC1 p.Arg706Trp (c.2116C>T)?

AlphaMissense predicts likely benign (score 0.162) — an in-silico prediction, not a clinical call.

EMC1 p.Arg706Trp

c.2116C>T · rs188945281 · VCV1417372

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.162 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.162	likely benign
REVEL	0.238	benign-leaning
SaProt	LLR -12.96	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 1.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 14 kb · p 4e-06 · 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 0.00223% East Asian · 1/44,878 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000929% 15/1,614,174 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,878
Admixed American	0.00167%	60,020
Remaining individualsnot grpmax-eligible	0.0016%	62,506
African / African-American	0.00133%	75,038
South Asian	0.0011%	91,086
European (non-Finnish)	0.000847%	118,003

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: EMC1
Protein: p.Arg706Trp
Coding: c.2116C>T
MANE Select: NM_015047
dbSNP: rs188945281
Type: single nucleotide variant
Location: chr1:19227399 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.67 · 10 PDB
Residue 706: a β-strand

Full EMC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EMC1 p.Arg706Gln Uncertain significance ★ ⚠ same residue
EMC1 p.Arg706= Likely benign ★ same residue
EMC1 c.287-1G>A Likely pathogenic ★★ same type
EMC1 c.787-1G>A Likely pathogenic ★★ same type
EMC1 p.Arg105Ter Pathogenic/Likely pathogenic ★★ same type
EMC1 p.Arg660Ter Pathogenic/Likely pathogenic ★★ same type
EMC1 p.Arg687Ter Pathogenic/Likely pathogenic ★★ same type
EMC1 p.Arg69Ter Pathogenic/Likely pathogenic ★★ 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/emc1-p-arg706trp (accessed [today's date]).

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