Is EFR3A p.Pro332= (c.996G>A) pathogenic?

EFR3A p.Pro332= (c.996G>A) is classified Likely benign in EFR3A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-31). Ultra-rare (popmax 0.0329%, mid); Associated with EFR3A-related disorder.

What condition is associated with EFR3A p.Pro332= (c.996G>A)?

EFR3A p.Pro332= (c.996G>A) is associated with EFR3A-related disorder (ClinVar).

How common is EFR3A p.Pro332= (c.996G>A) in the general population?

EFR3A p.Pro332= (c.996G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

EFR3A p.Pro332=

c.996G>A · rs376864937 · VCV3044754

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

EFR3A-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 -0.78	GERP -3.6, phastCons 0.003
Overall
CADD	5.654	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.00792% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00744%

Overall 0.00781% 126/1,613,230 alleles · ultra-rare exomes 118/1,461,090 · genomes 8/152,140 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
European (non-Finnish)	0.00941%	10,626
Remaining individualsnot grpmax-eligible	0.00801%	12,488
Admixed American	0.00501%	19,977
South Asian	0.0033%	30,332
African / African-American	0.00267%	37,455

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: EFR3A
Protein: p.Pro332=
Coding: c.996G>A
MANE Select: NM_015137
dbSNP: rs376864937
Type: single nucleotide variant
Location: chr8:131970480 (GRCh38)
Gene constraint: LOEUF 0.967 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.11 · 1 PDB

Full EFR3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EFR3A-related disorder

Similar variants

EFR3A p.Glu725Gly Uncertain significance ★ same condition
EFR3A p.Ile215Leu Uncertain significance ★ ⚠ same condition
EFR3A c.2065+1011C>T Likely benign same condition
EFR3A c.2311-9T>A Benign same condition
EFR3A c.639-3T>C Benign same condition
EFR3A c.856-9C>T Likely benign same condition
EFR3A p.Arg214His Likely benign same condition
EFR3A p.Asn181= 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/efr3a-p-pro332 (accessed [today's date]).

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