Is EFEMP1 p.Ser121Arg (c.363T>A) pathogenic?

EFEMP1 p.Ser121Arg (c.363T>A) is classified Uncertain significance in EFEMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-01). AlphaMissense: likely pathogenic (0.7241); Absent from gnomAD v4.1.

How common is EFEMP1 p.Ser121Arg (c.363T>A) in the general population?

EFEMP1 p.Ser121Arg (c.363T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFEMP1 p.Ser121Arg (c.363T>A)?

AlphaMissense predicts likely pathogenic (score 0.7241) — an in-silico prediction, not a clinical call.

EFEMP1 p.Ser121Arg

c.363T>A · VCV4729580

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7241 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7241	likely pathogenic
REVEL	0.232	benign-leaning
SaProt	LLR -8.91	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.061	GERP -5, phastCons 0.093
Regional constraint	o/e 0.76	unconstrained · MANE · 51 kb · p 1.9e-08 · regional, not allelic
Overall
CADD	14.27	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EFEMP1
Protein: p.Ser121Arg
Coding: c.363T>A
MANE Select: NM_001039348
Type: single nucleotide variant
Location: chr2:55917819 (GRCh38)
Gene constraint: LOEUF 0.373 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.67

Full EFEMP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFEMP1 p.Arg345Trp Pathogenic/Likely pathogenic ★★ same type
EFEMP1 p.Ala104Thr Uncertain significance ★★ ⚠ same type
EFEMP1 p.Ala126Pro Uncertain significance ★★ ⚠ same type
EFEMP1 p.Ala126Thr Uncertain significance ★★ ⚠ same type
EFEMP1 p.Ala447Ser Uncertain significance ★★ ⚠ same type
EFEMP1 p.Ala447Thr Uncertain significance ★★ ⚠ same type
EFEMP1 p.Arg148His Uncertain significance ★★ ⚠ same type
EFEMP1 p.Arg156Cys Uncertain significance ★★ ⚠ 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/efemp1-p-ser121arg (accessed [today's date]).

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