Is EFCAB13 p.Asp511fs (c.1530dup) pathogenic?

EFCAB13 p.Asp511fs (c.1530dup) is classified Likely benign in EFCAB13 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-01). Low-frequency (popmax 1.07%, sas); Associated with EFCAB13-related disorder.

What condition is associated with EFCAB13 p.Asp511fs (c.1530dup)?

EFCAB13 p.Asp511fs (c.1530dup) is associated with EFCAB13-related disorder (ClinVar).

How common is EFCAB13 p.Asp511fs (c.1530dup) in the general population?

EFCAB13 p.Asp511fs (c.1530dup) is low-frequency (popmax 1.07%, sas) (gnomAD).

EFCAB13 p.Asp511fs

c.1530dup · rs368918546 · VCV3042531

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

low-frequency (popmax 1.07%, sas)

Conditions

EFCAB13-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.1	phastCons 1
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.07% South Asian · 978/91,038 alleles

Filtering AF 1.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.996%

Overall 0.0641% 1,034/1,613,346 alleles · low-frequency exomes 977/1,460,998 · genomes 57/152,348 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.07%	93
Remaining individualsnot grpmax-eligible	0.0768%	1,301
Middle Eastern	0.0496%	2,018
African / African-American	0.00267%	37,516
European (non-Finnish)	0.000254%	393,159

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: EFCAB13
Protein: p.Asp511fs
Coding: c.1530dup
MANE Select: NM_152347
dbSNP: rs368918546
Type: Duplication
Location: chr17:47379200 (GRCh38)
Gene constraint: LOEUF 0.953 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
Structure: AlphaFold pLDDT 53.37
Residue 511: the ef-hand 1 domain

Full EFCAB13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EFCAB13-related disorder

Similar variants

EFCAB13 p.Gly650fs Benign same condition
EFCAB13 c.1802-9A>G Likely benign same condition
EFCAB13 c.1945+4_1945+7del Benign same condition
EFCAB13 c.806-1G>A Benign same condition
EFCAB13 p.Arg211Ter Benign same condition
EFCAB13 p.Arg236Ter Benign same condition
EFCAB13 p.Asn805= Benign same condition
EFCAB13 p.Asn968= Benign same condition

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/efcab13-p-asp511fs (accessed [today's date]).

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