Is EMC1 p.Arg401Trp (c.1201C>T) pathogenic?

EMC1 p.Arg401Trp (c.1201C>T) is classified Conflicting classifications of pathogenicity in EMC1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-20). AlphaMissense: likely benign (0.105); Rare (popmax 0.12%, sas).

How common is EMC1 p.Arg401Trp (c.1201C>T) in the general population?

EMC1 p.Arg401Trp (c.1201C>T) is rare (popmax 0.12%, sas) (gnomAD).

What do computational predictors say about EMC1 p.Arg401Trp (c.1201C>T)?

AlphaMissense predicts likely benign (score 0.105) — an in-silico prediction, not a clinical call.

EMC1 p.Arg401Trp

c.1201C>T · rs778418940 · VCV1010254

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.105 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.12%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.105	likely benign
REVEL	0.226	benign-leaning
SaProt	LLR -8.52	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 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 16 kb · p 0.24 · regional, not allelic
Overall
CADD	28.1	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 0.12% South Asian · 109/90,970 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0947%

Overall 0.00787% 127/1,613,640 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.12%	835
Remaining individualsnot grpmax-eligible	0.0128%	7,808
African / African-American	0.00534%	18,735
Admixed American	0.00167%	59,924
European (non-Finnish)	0.000424%	235,975

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.Arg401Trp
Coding: c.1201C>T
MANE Select: NM_015047
dbSNP: rs778418940
Type: single nucleotide variant
Location: chr1:19238028 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.67 · 10 PDB

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

Similar variants

EMC1 p.Arg401Gln 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
EMC1 p.Arg908Ter 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-arg401trp (accessed [today's date]).

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