Is EFCAB5 p.Ser671= (c.2013A>G) pathogenic?

EFCAB5 p.Ser671= (c.2013A>G) is classified Benign in EFCAB5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-11). Rare (popmax 0.561%, mid); Associated with EFCAB5-related disorder.

What condition is associated with EFCAB5 p.Ser671= (c.2013A>G)?

EFCAB5 p.Ser671= (c.2013A>G) is associated with EFCAB5-related disorder (ClinVar).

How common is EFCAB5 p.Ser671= (c.2013A>G) in the general population?

EFCAB5 p.Ser671= (c.2013A>G) is rare (popmax 0.561%, mid) (gnomAD).

EFCAB5 p.Ser671=

c.2013A>G · rs200049056 · VCV3041535

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.561%, mid)

Conditions

EFCAB5-related disorder

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 1.3	GERP -1.9
Overall
CADD	4.577	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.561% Middle Eastern · 34/6,062 alleles

Filtering AF 0.412% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.361%

Overall 0.0831% 1,341/1,613,874 alleles · rare exomes 1,183/1,461,502 · genomes 158/152,372 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.62%	38
Middle Easterngrpmax	0.561%	178
Remaining individualsnot grpmax-eligible	0.192%	521
Admixed American	0.0567%	1,764
European (non-Finnish)	0.0298%	3,361
South Asian	0.0176%	5,692
African / African-American	0.0147%	6,823

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: EFCAB5
Protein: p.Ser671=
Coding: c.2013A>G
MANE Select: NM_198529
dbSNP: rs200049056
Type: single nucleotide variant
Location: chr17:30053967 (GRCh38)
Gene constraint: LOEUF 0.908 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.22

Full EFCAB5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EFCAB5-related disorder

Similar variants

EFCAB5 c.2365+5A>G Likely benign same condition
EFCAB5 c.2738-5079G>A Likely benign same condition
EFCAB5 c.3198-8T>C Likely benign same condition
EFCAB5 p.Ala1120Ser Likely benign same condition
EFCAB5 p.Arg561Ser Benign same condition
EFCAB5 p.Cys800Phe Benign same condition
EFCAB5 p.Gln481Glu Benign same condition
EFCAB5 p.Glu64Gly Likely 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/efcab5-p-ser671 (accessed [today's date]).

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