Is DISP1 p.Phe552= (c.1656C>T) pathogenic?

DISP1 p.Phe552= (c.1656C>T) is classified Likely benign in DISP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-13). Very rare (popmax 0.00169%, nfe).

How common is DISP1 p.Phe552= (c.1656C>T) in the general population?

DISP1 p.Phe552= (c.1656C>T) is very rare (popmax 0.00169%, nfe) (gnomAD).

DISP1 p.Phe552=

c.1656C>T · rs753258388 · VCV2191445

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00169%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8
Overall
CADD	1.247	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00169% European (non-Finnish) · 20/1,180,034 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00171% 25/1,461,832 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,829
European (non-Finnish)grpmax	0.00169%	59,002
Admixed American	0.00167%	59,994
South Asian	0.0011%	91,076

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DISP1
Protein: p.Phe552=
Coding: c.1656C>T
MANE Select: NM_001377229
dbSNP: rs753258388
Type: single nucleotide variant
Location: chr1:223003053 (GRCh38)
Gene constraint: LOEUF 1.028 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 65.21 · 4 PDB
Residue 552: the ssd domain; a UniProt-annotated variant site (in hpe10; uncertain significance; heterozygous variant inherited from unaffected parent); a UniProt-annotated variant site (in hpe10; uncertain significance; heterozygous variant inherited from unaffected parent; the orthologous mouse mutation results in severely decreased extracellular release of shh)

Full DISP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DISP1 p.Ala1123Thr Uncertain significance ★★ ⚠ same type
DISP1 p.Ala1204Thr Uncertain significance ★★ ⚠ same type
DISP1 p.Ala248Val Uncertain significance ★★ ⚠ same type
DISP1 p.Ala733Val Uncertain significance ★★ ⚠ same type
DISP1 p.Arg1061His Uncertain significance ★★ ⚠ same type
DISP1 p.Arg718His Uncertain significance ★★ ⚠ same type
DISP1 p.Arg763His Uncertain significance ★★ ⚠ same type
DISP1 p.Asn1035Ser 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/disp1-p-phe552 (accessed [today's date]).

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