Is EMC1 p.Ser596Leu (c.1787C>T) pathogenic?

EMC1 p.Ser596Leu (c.1787C>T) is classified Benign/Likely benign in EMC1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1325); Low-frequency (popmax 1.28%, afr); Associated with inherited retinal dystrophy.

What condition is associated with EMC1 p.Ser596Leu (c.1787C>T)?

EMC1 p.Ser596Leu (c.1787C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is EMC1 p.Ser596Leu (c.1787C>T) in the general population?

EMC1 p.Ser596Leu (c.1787C>T) is low-frequency (popmax 1.28%, afr) (gnomAD).

What do computational predictors say about EMC1 p.Ser596Leu (c.1787C>T)?

AlphaMissense predicts likely benign (score 0.1325) — an in-silico prediction, not a clinical call.

EMC1 p.Ser596Leu

c.1787C>T · rs140940082 · VCV710872

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1325 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.28%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.1325	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -8.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 14 kb · p 4e-06 · regional, not allelic
Overall
CADD	22.2	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 1.28% African / African-American · 960/74,772 alleles

Filtering AF 1.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.19%

Overall 0.0711% 1,146/1,611,634 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.28%	78
Admixed American	0.157%	636
Remaining individualsnot grpmax-eligible	0.0945%	1,058
East Asian	0.0491%	2,036
South Asian	0.0011%	90,700
European (non-Finnish)	0.000933%	107,216

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.Ser596Leu
Coding: c.1787C>T
dbSNP: rs140940082
Type: single nucleotide variant
Location: chr1:19231418 (GRCh38)

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-ser596leu (accessed [today's date]).

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