Is MEN1 p.Asp172Val (c.515A>T) pathogenic?

MEN1 p.Asp172Val (c.515A>T) is classified Likely pathogenic in MEN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-04-14). AlphaMissense: likely pathogenic (0.9977); Very rare (popmax 6.84e-05%); Associated with hereditary neoplastic syndrome.

What condition is associated with MEN1 p.Asp172Val (c.515A>T)?

MEN1 p.Asp172Val (c.515A>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MEN1 p.Asp172Val (c.515A>T) in the general population?

MEN1 p.Asp172Val (c.515A>T) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about MEN1 p.Asp172Val (c.515A>T)?

AlphaMissense predicts likely pathogenic (score 0.9977) — an in-silico prediction, not a clinical call.

MEN1 p.Asp172Val

c.515A>T · rs794728618 · VCV200973

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9977 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9977	likely pathogenic ✓ concordant with ClinVar
REVEL	0.938	strongly pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 4,962 bp · p 4.4e-20 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D177V vs ClinVar D172V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,860 alleles · very rare

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: MEN1
Protein: p.Asp172Val
Coding: c.515A>T
MANE Select: NM_001370259
dbSNP: rs794728618
Type: single nucleotide variant
Location: chr11:64808030 (GRCh38)
Gene constraint: LOEUF 0.206 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.13 · 69 PDB
Residue 172: a UniProt-annotated variant site (in men1)

Full MEN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MEN1 p.Asp172Tyr Pathogenic/Likely pathogenic ★★ same residue
MEN1 p.Asp172= Likely benign ★★ same residue
MEN1 p.Asp172His Uncertain significance ★ ⚠ same residue
MEN1 c.1049+1G>A Pathogenic ★★ same condition
MEN1 c.1049+1G>C Pathogenic ★★ same condition
MEN1 c.1350+1G>A Pathogenic ★★ same condition
MEN1 c.1351-2A>C Pathogenic/Likely pathogenic ★★ same condition
MEN1 c.446-1G>A Pathogenic ★★ 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/men1-p-asp172val (accessed [today's date]).

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