Is DISP2 p.Phe837Leu (c.2511C>G) pathogenic?

DISP2 p.Phe837Leu (c.2511C>G) is classified Uncertain significance in DISP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-29). AlphaMissense: ambiguous (0.5265); Ultra-rare (popmax 0.0546%, afr).

How common is DISP2 p.Phe837Leu (c.2511C>G) in the general population?

DISP2 p.Phe837Leu (c.2511C>G) is ultra-rare (popmax 0.0546%, afr) (gnomAD).

What do computational predictors say about DISP2 p.Phe837Leu (c.2511C>G)?

AlphaMissense predicts ambiguous (score 0.5265) — an in-silico prediction, not a clinical call.

DISP2 p.Phe837Leu

c.2511C>G · rs201602512 · VCV2599523

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5265 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0546%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5265	ambiguous
REVEL	0.057	moderately benign-leaning
SaProt	LLR -4.87	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.97	GERP -2.5
Regional constraint	o/e 0.80	unconstrained · MANE · 918 bp · p 8.8e-05 · regional, not allelic
Overall
CADD	5.922	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 0.0546% African / African-American · 41/75,072 alleles

Filtering AF 0.0413% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0367%

Overall 0.0087% 140/1,608,288 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0546%	1,831
European (non-Finnish)	0.00805%	12,421
Remaining individualsnot grpmax-eligible	0.0064%	15,616

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.Phe837Leu
Coding: c.2511C>G
MANE Select: NM_033510
dbSNP: rs201602512
Type: single nucleotide variant
Location: chr15:40368623 (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-phe837leu (accessed [today's date]).

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