Is SUN2 p.Thr571Met (c.1712C>T) pathogenic?

SUN2 p.Thr571Met (c.1712C>T) is classified Uncertain significance in SUN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-20). AlphaMissense: likely benign (0.3231); Very rare (popmax 0.00935%, afr); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 p.Thr571Met (c.1712C>T)?

SUN2 p.Thr571Met (c.1712C>T) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN2 p.Thr571Met (c.1712C>T) in the general population?

SUN2 p.Thr571Met (c.1712C>T) is very rare (popmax 0.00935%, afr) (gnomAD).

How is Emery-Dreifuss muscular dystrophy inherited?

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

What do computational predictors say about SUN2 p.Thr571Met (c.1712C>T)?

AlphaMissense predicts likely benign (score 0.3231) — an in-silico prediction, not a clinical call.

SUN2 p.Thr571Met

c.1712C>T · rs752150588 · VCV566584

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3231 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Emery-Dreifuss muscular dystrophy

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.3231	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -11.33	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 8.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 2,037 bp · p 3.5e-07 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00935% African / African-American · 7/74,906 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00112% 18/1,613,536 alleles · very rare exomes 15/1,461,410 · genomes 3/152,126 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,701
Finnishnot grpmax-eligible	0.00313%	31,990
South Asian	0.0011%	91,012
European (non-Finnish)	0.000678%	147,476

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: SUN2
Protein: p.Thr571Met
Coding: c.1712C>T
MANE Select: NM_015374
dbSNP: rs752150588
Type: single nucleotide variant
Location: chr22:38738940 (GRCh38)

Full SUN2 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)

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/sun2-p-thr571met (accessed [today's date]).

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