Is DISP2 p.Val172Met (c.514G>A) pathogenic?

DISP2 p.Val172Met (c.514G>A) is classified Uncertain significance in DISP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). AlphaMissense: likely benign (0.1007); Very rare (popmax 0.00446%, eas).

How common is DISP2 p.Val172Met (c.514G>A) in the general population?

DISP2 p.Val172Met (c.514G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about DISP2 p.Val172Met (c.514G>A)?

AlphaMissense predicts likely benign (score 0.1007) — an in-silico prediction, not a clinical call.

DISP2 p.Val172Met

c.514G>A · VCV3840207

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1007 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1007	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -10.22	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.66	GERP -3.7, phastCons 0.045
Regional constraint	o/e 0.94	unconstrained · MANE · 6,941 bp · p 0.24 · regional, not allelic
Overall
CADD	15.62	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 0.00446% East Asian · 2/44,888 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00235% 38/1,613,884 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,444
Remaining individualsnot grpmax-eligible	0.0032%	31,241
European (non-Finnish)	0.00263%	38,066
South Asian	0.0022%	45,547
African / African-American	0.00133%	74,940

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: DISP2
Protein: p.Val172Met
Coding: c.514G>A
MANE Select: NM_033510
Type: single nucleotide variant
Location: chr15:40364455 (GRCh38)
Gene constraint: LOEUF 0.813 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.24

Full DISP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DISP2 p.Pro194= Benign ★★ same type
DISP2 p.Ala1053Thr Uncertain significance ★ ⚠ same type
DISP2 p.Ala1069Gly Uncertain significance ★ ⚠ same type
DISP2 p.Ala1128Ser Uncertain significance ★ ⚠ same type
DISP2 p.Ala1128Val Uncertain significance ★ ⚠ same type
DISP2 p.Ala1210Gly Uncertain significance ★ ⚠ same type
DISP2 p.Ala1343Pro Uncertain significance ★ ⚠ same type
DISP2 p.Ala1343Val 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/disp2-p-val172met (accessed [today's date]).

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