Is EFL1 p.Pro606= (c.1818A>G) pathogenic?

EFL1 p.Pro606= (c.1818A>G) is classified Likely benign in EFL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-21). Ultra-rare (popmax 0.0297%, nfe).

How common is EFL1 p.Pro606= (c.1818A>G) in the general population?

EFL1 p.Pro606= (c.1818A>G) is ultra-rare (popmax 0.0297%, nfe) (gnomAD).

EFL1 p.Pro606=

c.1818A>G · rs760435290 · VCV1563801

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0297%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -4.5
Overall
CADD	0.059	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0297% European (non-Finnish) · 351/1,180,018 alleles

Filtering AF 0.0271% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0262%

Overall 0.0235% 379/1,613,978 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0336%	2,976
European (non-Finnish)grpmax	0.0297%	3,362
Middle Eastern	0.0164%	6,084
East Asian	0.00669%	14,959
African / African-American	0.00267%	37,452
Admixed American	0.00167%	59,988

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: EFL1
Protein: p.Pro606=
Coding: c.1818A>G
MANE Select: NM_024580
dbSNP: rs760435290
Type: single nucleotide variant
Location: chr15:82163917 (GRCh38)
Gene constraint: LOEUF 0.718 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.72 · 2 PDB

Full EFL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFL1 c.1444+3A>C Uncertain significance ★★ same type
EFL1 c.244+2T>G Uncertain significance ★★ same type
EFL1 p.Ala755Thr Uncertain significance ★★ ⚠ same type
EFL1 p.Arg108His Uncertain significance ★★ ⚠ same type
EFL1 p.Arg1097Trp Uncertain significance ★★ ⚠ same type
EFL1 p.Arg330Trp Uncertain significance ★★ ⚠ same type
EFL1 p.Arg444His Uncertain significance ★★ ⚠ same type
EFL1 p.Arg970Cys 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/efl1-p-pro606 (accessed [today's date]).

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