Is EFEMP2 p.Tyr441= (c.1323C>T) pathogenic?

EFEMP2 p.Tyr441= (c.1323C>T) is classified Likely benign in EFEMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-18). Very rare (popmax 0.00267%, afr); Associated with Cardiovascular phenotype.

What condition is associated with EFEMP2 p.Tyr441= (c.1323C>T)?

EFEMP2 p.Tyr441= (c.1323C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is EFEMP2 p.Tyr441= (c.1323C>T) in the general population?

EFEMP2 p.Tyr441= (c.1323C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

EFEMP2 p.Tyr441=

c.1323C>T · rs1194617277 · VCV1769946

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.116	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -0.42, phastCons 0.98
Overall
CADD	7.292	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/75,032 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,614,156 alleles · very rare exomes 2/1,461,856 · genomes 0/152,300 · joint denominator

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: EFEMP2
Protein: p.Tyr441=
Coding: c.1323C>T
MANE Select: NM_016938
dbSNP: rs1194617277
Type: single nucleotide variant
Location: chr11:65866927 (GRCh38)
Gene constraint: LOEUF 0.56 · pLI 0.62 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 1 PDB

Full EFEMP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EFEMP2 p.Glu167Ter Pathogenic ★★ same condition
EFEMP2 c.608-3C>G Uncertain significance ★★ same condition
EFEMP2 p.Ala103Thr Uncertain significance ★★ ⚠ same condition
EFEMP2 p.Ala291Gly Uncertain significance ★★ ⚠ same condition
EFEMP2 p.Ala85Thr Uncertain significance ★★ ⚠ same condition
EFEMP2 p.Ala86Thr Uncertain significance ★★ ⚠ same condition
EFEMP2 p.Arg156Cys Uncertain significance ★★ ⚠ same condition
EFEMP2 p.Arg169Cys Uncertain significance ★★ ⚠ same condition

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/efemp2-p-tyr441 (accessed [today's date]).

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