Is EFL1 p.Pro627= (c.1881A>G) pathogenic?

EFL1 p.Pro627= (c.1881A>G) is classified Likely benign in EFL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-02). Ultra-rare (popmax 0.0814%, sas).

How common is EFL1 p.Pro627= (c.1881A>G) in the general population?

EFL1 p.Pro627= (c.1881A>G) is ultra-rare (popmax 0.0814%, sas) (gnomAD).

EFL1 p.Pro627=

c.1881A>G · rs570887120 · VCV1486237

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0814%, sas)

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 0.17	GERP -0.19, phastCons 0.99
Overall
CADD	13.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0814% South Asian · 74/90,902 alleles

Filtering AF 0.0664% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0609%

Overall 0.00508% 82/1,613,662 alleles · ultra-rare exomes 76/1,461,334 · genomes 6/152,328 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0814%	1,228
Remaining individualsnot grpmax-eligible	0.0112%	8,926
European (non-Finnish)	8.48e-05%	1,179,878

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.Pro627=
Coding: c.1881A>G
MANE Select: NM_024580
dbSNP: rs570887120
Type: single nucleotide variant
Location: chr15:82163854 (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-pro627 (accessed [today's date]).

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