Is EFL1 p.Phe612= (c.1836C>T) pathogenic?

EFL1 p.Phe612= (c.1836C>T) is classified Benign/Likely benign in EFL1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-26). Rare (popmax 0.178%, eas).

How common is EFL1 p.Phe612= (c.1836C>T) in the general population?

EFL1 p.Phe612= (c.1836C>T) is rare (popmax 0.178%, eas) (gnomAD).

EFL1 p.Phe612=

c.1836C>T · rs377357859 · VCV1633633

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.178%, eas)

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 -3.8	GERP -4.5
Overall
CADD	6.222	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.178% East Asian · 80/44,882 alleles

Filtering AF 0.147% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.135%

Overall 0.00719% 116/1,614,128 alleles · rare exomes 94/1,461,818 · genomes 22/152,310 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.178%	561
Remaining individualsnot grpmax-eligible	0.0096%	10,418
South Asian	0.00439%	22,769
European (non-Finnish)	0.00212%	47,200
Admixed American	0.00167%	60,016

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.Phe612=
Coding: c.1836C>T
MANE Select: NM_024580
dbSNP: rs377357859
Type: single nucleotide variant
Location: chr15:82163899 (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-phe612 (accessed [today's date]).

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