Is EFL1 p.Ala968= (c.2904A>G) pathogenic?

EFL1 p.Ala968= (c.2904A>G) is classified Likely benign in EFL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-15). Very rare (popmax 0.00133%, afr).

How common is EFL1 p.Ala968= (c.2904A>G) in the general population?

EFL1 p.Ala968= (c.2904A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

EFL1 p.Ala968=

c.2904A>G · rs1464923508 · VCV2974714

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -11	GERP -5.4
Overall
CADD	0.165	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,056 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,614,190 alleles · very rare exomes 4/1,461,884 · genomes 0/152,306 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,056
European (non-Finnish)	0.000254%	393,343

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.Ala968=
Coding: c.2904A>G
MANE Select: NM_024580
dbSNP: rs1464923508
Type: single nucleotide variant
Location: chr15:82151550 (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 p.Ala968Ser Uncertain significance ★ ⚠ same residue
EFL1 p.Ala968Thr Uncertain significance ★ ⚠ same residue
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

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-ala968 (accessed [today's date]).

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