Is EMC1 p.Phe670Leu (c.2008T>C) pathogenic?

EMC1 p.Phe670Leu (c.2008T>C) is classified Conflicting classifications of pathogenicity in EMC1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-08-20). AlphaMissense: likely pathogenic (0.9192); Rare (popmax 0.236%, eas); Associated with inherited retinal dystrophy.

What condition is associated with EMC1 p.Phe670Leu (c.2008T>C)?

EMC1 p.Phe670Leu (c.2008T>C) is associated with inherited retinal dystrophy, cerebellar atrophy, visual impairment, and psychomotor retardation; (ClinVar).

How common is EMC1 p.Phe670Leu (c.2008T>C) in the general population?

EMC1 p.Phe670Leu (c.2008T>C) is rare (popmax 0.236%, eas) (gnomAD).

What do computational predictors say about EMC1 p.Phe670Leu (c.2008T>C)?

AlphaMissense predicts likely pathogenic (score 0.9192) — an in-silico prediction, not a clinical call.

EMC1 p.Phe670Leu

c.2008T>C · rs2275402 · VCV1475136

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9192 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.236%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.9192	likely pathogenic
REVEL	0.414	indeterminate
SaProt	LLR -9.22	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 14 kb · p 4e-06 · regional, not allelic
Overall
CADD	27.6	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 0.236% East Asian · 106/44,882 alleles

Filtering AF 0.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.186%

Overall 0.00694% 112/1,614,218 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.236%	423
Remaining individualsnot grpmax-eligible	0.008%	12,502
European (non-Finnish)	8.47e-05%	1,180,043

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.Phe670Leu
Coding: c.2008T>C
dbSNP: rs2275402
Type: single nucleotide variant
Location: chr1:19230900 (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

Also linked: cerebellar atrophy, visual impairment, and psychomotor retardation;

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-phe670leu (accessed [today's date]).

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