Is EFEMP1 p.Ser106Arg (c.318C>G) pathogenic?

EFEMP1 p.Ser106Arg (c.318C>G) is classified Uncertain significance in EFEMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-22). AlphaMissense: likely pathogenic (0.6333); Very rare (popmax 0.00195%, nfe).

How common is EFEMP1 p.Ser106Arg (c.318C>G) in the general population?

EFEMP1 p.Ser106Arg (c.318C>G) is very rare (popmax 0.00195%, nfe) (gnomAD).

What do computational predictors say about EFEMP1 p.Ser106Arg (c.318C>G)?

AlphaMissense predicts likely pathogenic (score 0.6333) — an in-silico prediction, not a clinical call.

EFEMP1 p.Ser106Arg

c.318C>G · rs369150030 · VCV1914157

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6333 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00195%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6333	likely pathogenic
REVEL	0.136	moderately benign-leaning
SaProt	LLR -9.12	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 0.84	GERP -1.2, phastCons 0.73
Regional constraint	o/e 0.76	unconstrained · MANE · 51 kb · p 1.9e-08 · regional, not allelic
Overall
CADD	13.01	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 0.00195% European (non-Finnish) · 23/1,180,056 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00142% 23/1,614,138 alleles · very rare

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: EFEMP1
Protein: p.Ser106Arg
Coding: c.318C>G
MANE Select: NM_001039348
dbSNP: rs369150030
Type: single nucleotide variant
Location: chr2:55917864 (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.Ser106Ile Uncertain significance ★ ⚠ same residue
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

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-ser106arg (accessed [today's date]).

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