Is SUN5 p.Ala84Val (c.251C>T) pathogenic?

SUN5 p.Ala84Val (c.251C>T) is classified Uncertain significance in SUN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-15). AlphaMissense: likely benign (0.0942); Ultra-rare (popmax 0.031%, nfe).

How common is SUN5 p.Ala84Val (c.251C>T) in the general population?

SUN5 p.Ala84Val (c.251C>T) is ultra-rare (popmax 0.031%, nfe) (gnomAD).

What do computational predictors say about SUN5 p.Ala84Val (c.251C>T)?

AlphaMissense predicts likely benign (score 0.0942) — an in-silico prediction, not a clinical call.

SUN5 p.Ala84Val

c.251C>T · rs775572724 · VCV2334796

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0942 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.031%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0942	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -5.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.069	GERP -3.7
Regional constraint	o/e 0.90	unconstrained · MANE · 21 kb · p 0.021 · regional, not allelic
Overall
CADD	3.421	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.031% European (non-Finnish) · 359/1,159,636 alleles

Filtering AF 0.0283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0272%

Overall 0.0234% 369/1,578,316 alleles · ultra-rare exomes 346/1,426,150 · genomes 23/152,166 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.031%	3,230
Remaining individualsnot grpmax-eligible	0.0131%	7,633
Admixed American	0.00179%	55,854
African / African-American	0.00135%	74,320

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: SUN5
Protein: p.Ala84Val
Coding: c.251C>T
MANE Select: NM_080675
dbSNP: rs775572724
Type: single nucleotide variant
Location: chr20:33001239 (GRCh38)
Gene constraint: LOEUF 1.146 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.31

Full SUN5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SUN5 p.Arg356Cys Likely pathogenic ★★ same type
SUN5 p.Arg149Ter Likely pathogenic ★ same type
SUN5 c.984+8C>T Uncertain significance ★ same type
SUN5 p.Ala206= Uncertain significance ★ same type
SUN5 p.Ala28Ser Uncertain significance ★ ⚠ same type
SUN5 p.Ala364Ser Uncertain significance ★ ⚠ same type
SUN5 p.Ala59Thr Uncertain significance ★ ⚠ same type
SUN5 p.Arg30Gln Uncertain significance ★ ⚠ same type

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/sun5-p-ala84val (accessed [today's date]).

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