Is EGFL7 p.Arg202Lys (c.605G>A) pathogenic?

EGFL7 p.Arg202Lys (c.605G>A) is classified Uncertain significance in EGFL7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-15). AlphaMissense: likely benign (0.0998); Ultra-rare (popmax 0.0137%, amr).

How common is EGFL7 p.Arg202Lys (c.605G>A) in the general population?

EGFL7 p.Arg202Lys (c.605G>A) is ultra-rare (popmax 0.0137%, amr) (gnomAD).

What do computational predictors say about EGFL7 p.Arg202Lys (c.605G>A)?

AlphaMissense predicts likely benign (score 0.0998) — an in-silico prediction, not a clinical call.

EGFL7 p.Arg202Lys

c.605G>A · VCV4016649

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0998 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0137%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0998	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -8.20	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 2.2	GERP -3.2, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 4,000 bp · p 0.79 · regional, not allelic
Overall
CADD	3.48	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 0.0137% Admixed American · 7/51,248 alleles

Filtering AF 0.00636% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.000586% 8/1,364,786 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0137%	7,321
South Asian	0.00118%	84,672

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: EGFL7
Protein: p.Arg202Lys
Coding: c.605G>A
MANE Select: NM_016215
Type: single nucleotide variant
Location: chr9:136670983 (GRCh38)
Gene constraint: LOEUF 1.797 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.11

Full EGFL7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EGFL7 p.Arg112Gln Benign/Likely benign ★★ same type
EGFL7 p.Ala101Asp Uncertain significance ★ ⚠ same type
EGFL7 p.Ala104Thr Uncertain significance ★ ⚠ same type
EGFL7 p.Ala143Thr Uncertain significance ★ ⚠ same type
EGFL7 p.Ala156Thr Uncertain significance ★ ⚠ same type
EGFL7 p.Ala87Thr Uncertain significance ★ ⚠ same type
EGFL7 p.Ala87Val Uncertain significance ★ ⚠ same type
EGFL7 p.Arg124Cys 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/egfl7-p-arg202lys (accessed [today's date]).

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