Is EFEMP1 p.Ile191Val (c.571A>G) pathogenic?

EFEMP1 p.Ile191Val (c.571A>G) is classified Uncertain significance in EFEMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-11). AlphaMissense: likely benign (0.0741); Very rare (popmax 0.00333%, amr).

How common is EFEMP1 p.Ile191Val (c.571A>G) in the general population?

EFEMP1 p.Ile191Val (c.571A>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about EFEMP1 p.Ile191Val (c.571A>G)?

AlphaMissense predicts likely benign (score 0.0741) — an in-silico prediction, not a clinical call.

EFEMP1 p.Ile191Val

c.571A>G · rs967298053 · VCV850570

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0741 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0741	likely benign
REVEL	0.257	benign-leaning
SaProt	LLR -5.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.069	GERP -5.2, phastCons 0.97
Regional constraint	o/e 0.76	unconstrained · MANE · 51 kb · p 1.9e-08 · regional, not allelic
Overall
CADD	8.718	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,008 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000137% 2/1,461,710 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.Ile191Val
Coding: c.571A>G
MANE Select: NM_001039348
dbSNP: rs967298053
Type: single nucleotide variant
Location: chr2:55881681 (GRCh38)
Gene constraint: LOEUF 0.373 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.67
Residue 191: a disulfide bond; the egf-like 2; calcium-binding domain

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

Similar variants

EFEMP1 p.Ile191Thr 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-ile191val (accessed [today's date]).

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