Is EFL1 p.Asp952= (c.2856C>T) pathogenic?

EFL1 p.Asp952= (c.2856C>T) is classified Benign/Likely benign in EFL1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 54.9%, afr) — too common for a highly-penetrant pathogenic allele.

EFL1 p.Asp952=

Q: How common is EFL1 p.Asp952= (c.2856C>T) in the general population?

EFL1 p.Asp952= (c.2856C>T) is common (popmax 54.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2856C>T · rs4725 · VCV1166425

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 54.9%, afr) — too common for a highly-penetrant pathogenic allele

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 6.6	GERP 1.9, phastCons 1
Overall
CADD	6.613	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 54.9% African / African-American · 41,115/74,888 alleles

Filtering AF 54.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 54.3%

Overall 30.2% 488,155/1,613,878 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	54.9%	2
Ashkenazi Jewishnot grpmax-eligible	37.8%	3
Middle Eastern	35.3%	3
European (non-Finnish)	30.8%	3
Remaining individualsnot grpmax-eligible	30.6%	3
Amishnot grpmax-eligible	23.7%	4
Finnishnot grpmax-eligible	23.6%	4
Admixed American	20%	5
East Asian	19.7%	5
South Asian	15.9%	6

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.Asp952=
Coding: c.2856C>T
MANE Select: NM_024580
dbSNP: rs4725
Type: single nucleotide variant
Location: chr15:82151598 (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-asp952 (accessed [today's date]).

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