Is SUN2 p.Ala162Val (c.485C>T) pathogenic?

SUN2 p.Ala162Val (c.485C>T) is classified Benign in SUN2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0818); Low-frequency (popmax 1.61%, afr); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 p.Ala162Val (c.485C>T)?

SUN2 p.Ala162Val (c.485C>T) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN2 p.Ala162Val (c.485C>T) in the general population?

SUN2 p.Ala162Val (c.485C>T) is low-frequency (popmax 1.61%, 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.Ala162Val (c.485C>T)?

AlphaMissense predicts likely benign (score 0.0818) — an in-silico prediction, not a clinical call.

SUN2 p.Ala162Val

c.485C>T · rs62639696 · VCV461688

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0818 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.61%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.0818	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -6.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.61	donor gain · deltas
Constraint at this position
Conservation	phyloP 0.53	GERP -4.6, phastCons 0.001
Regional constraint	o/e 0.94	unconstrained · MANE · 12 kb · p 0.11 · regional, not allelic
Overall
CADD	13.3	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 1.61% African / African-American · 1,212/75,054 alleles

Filtering AF 1.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.51%

Overall 0.0824% 1,329/1,613,740 alleles · low-frequency exomes 686/1,461,404 · genomes 643/152,336 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.61%	62
Middle Eastern	0.099%	1,010
Remaining individualsnot grpmax-eligible	0.088%	1,136
Admixed American	0.0416%	2,401
South Asian	0.00329%	30,363
European (non-Finnish)	0.00237%	42,138

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.Ala162Val
Coding: c.485C>T
MANE Select: NM_015374
dbSNP: rs62639696
Type: single nucleotide variant
Location: chr22:38750260 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.48 · 9 PDB

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)

Similar variants

SUN2 p.Ala162= Likely benign ★ same residue
SUN2 p.Ala158Thr Uncertain significance ★★ ⚠ same condition
SUN2 p.Ala251Val Uncertain significance ★★ ⚠ same condition
SUN2 p.Ala508Val Uncertain significance ★★ ⚠ same condition
SUN2 p.Ala56Val Uncertain significance ★★ ⚠ same condition
SUN2 p.Arg100Gln Uncertain significance ★★ ⚠ same condition
SUN2 p.Arg102Gln Uncertain significance ★★ ⚠ same condition
SUN2 p.Arg102Trp 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/sun2-p-ala162val (accessed [today's date]).

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