Is EMC1 p.Pro240Leu (c.719C>T) pathogenic?

EMC1 p.Pro240Leu (c.719C>T) is classified Benign/Likely benign in EMC1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0877); Low-frequency (popmax 1.33%, afr).

How common is EMC1 p.Pro240Leu (c.719C>T) in the general population?

EMC1 p.Pro240Leu (c.719C>T) is low-frequency (popmax 1.33%, afr) (gnomAD).

What do computational predictors say about EMC1 p.Pro240Leu (c.719C>T)?

AlphaMissense predicts likely benign (score 0.0877) — an in-silico prediction, not a clinical call.

EMC1 p.Pro240Leu

c.719C>T · rs141614470 · VCV446000

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0877 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.33%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0877	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -3.96	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 4.6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 16 kb · p 0.24 · regional, not allelic
Overall
CADD	22.9	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 1.33% African / African-American · 1,001/75,028 alleles

Filtering AF 1.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.24%

Overall 0.132% 2,123/1,614,164 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.33%	75
Middle Eastern	0.495%	202
Admixed American	0.387%	259
Remaining individualsnot grpmax-eligible	0.269%	372
European (non-Finnish)	0.0575%	1,740
South Asian	0.00988%	10,121
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803
Finnishnot grpmax-eligible	0.00469%	21,343

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.Pro240Leu
Coding: c.719C>T
MANE Select: NM_015047
dbSNP: rs141614470
Type: single nucleotide variant
Location: chr1:19240364 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.67 · 10 PDB
Residue 240: a turn

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

Similar variants

EMC1 p.Pro240Gln Uncertain significance ★ ⚠ same residue
EMC1 p.Pro240= 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-pro240leu (accessed [today's date]).

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