Is SUN2 p.Val408Met (c.1222G>A) pathogenic?

SUN2 p.Val408Met (c.1222G>A) is classified Likely benign in SUN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely benign (0.0825); Ultra-rare (popmax 0.0336%, mid).

How common is SUN2 p.Val408Met (c.1222G>A) in the general population?

SUN2 p.Val408Met (c.1222G>A) is ultra-rare (popmax 0.0336%, mid) (gnomAD).

What do computational predictors say about SUN2 p.Val408Met (c.1222G>A)?

AlphaMissense predicts likely benign (score 0.0825) — an in-silico prediction, not a clinical call.

SUN2 p.Val408Met

c.1222G>A · VCV4177764

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0825 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0336%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ 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	0.0825	likely benign
REVEL	0.005	strongly benign-leaning
SaProt	LLR -6.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -4	GERP -4.1
Regional constraint	o/e 0.94	unconstrained · MANE · 12 kb · p 0.11 · regional, not allelic
Overall
CADD	3.84	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 0.0336% Middle Eastern · 2/5,948 alleles

Filtering AF 0.00592% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00246%

Overall 0.000128% 2/1,567,886 alleles · ultra-rare exomes 2/1,415,590 · genomes 0/152,296 · joint denominator

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.Val408Met
Coding: c.1222G>A
MANE Select: NM_015374
Type: single nucleotide variant
Location: chr22:38740401 (GRCh38)

Full SUN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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-val408met (accessed [today's date]).

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