Is SUN1 p.Thr38= (c.114G>A) pathogenic?

SUN1 p.Thr38= (c.114G>A) is classified Benign in SUN1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-30). Common (popmax 15.1%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN1 p.Thr38= (c.114G>A)?

SUN1 p.Thr38= (c.114G>A) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How is Emery-Dreifuss muscular dystrophy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SUN1 p.Thr38=

Q: How common is SUN1 p.Thr38= (c.114G>A) in the general population?

SUN1 p.Thr38= (c.114G>A) is common (popmax 15.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.114G>A · rs76073621 · VCV461639

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 15.1%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

Emery-Dreifuss muscular dystrophy

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 -4.5	GERP -3.2
Overall
CADD	3.612	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15.1% East Asian · 6,473/42,994 alleles

Filtering AF 14.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.6%

Overall 0.614% 9,613/1,566,222 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	15.1%	7
Finnishnot grpmax-eligible	2.09%	48
Remaining individualsnot grpmax-eligible	0.814%	123
South Asian	0.382%	262
Ashkenazi Jewishnot grpmax-eligible	0.304%	329
Middle Eastern	0.267%	375
European (non-Finnish)	0.0776%	1,289
Admixed American	0.0539%	1,856
African / African-American	0.0175%	5,718

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: SUN1
Protein: p.Thr38=
Coding: c.114G>A
MANE Select: NM_001130965
dbSNP: rs76073621
Type: single nucleotide variant
Location: chr7:838834 (GRCh38)
Gene constraint: LOEUF 0.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99 · 8 PDB
Residue 38: the 'lmna-binding' region

Full SUN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Emery-Dreifuss muscular dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Emery-Dreifuss muscular dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

SUN1 p.Thr38Met Uncertain significance ★ same residue
SUN1 p.Ala179Thr Uncertain significance ★★ same condition
SUN1 p.Ala203Thr Uncertain significance ★★ same condition
SUN1 p.Ala232Val Uncertain significance ★★ same condition
SUN1 p.Ala236Thr Uncertain significance ★★ same condition
SUN1 p.Ala255Thr Uncertain significance ★★ same condition
SUN1 p.Ala256Val Uncertain significance ★★ same condition
SUN1 p.Ala404Thr Uncertain significance ★★ 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/sun1-p-thr38 (accessed [today's date]).

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