Is DDR2 p.Ser504= (c.1512C>T) pathogenic?

DDR2 p.Ser504= (c.1512C>T) is classified Likely benign in DDR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-17). Very rare (popmax 0.00936%, afr).

How common is DDR2 p.Ser504= (c.1512C>T) in the general population?

DDR2 p.Ser504= (c.1512C>T) is very rare (popmax 0.00936%, afr) (gnomAD).

DDR2 p.Ser504=

c.1512C>T · rs199900233 · VCV1628475

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00936%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.337	indeterminate
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.9	GERP -3.3
Overall
CADD	4.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00936% African / African-American · 7/74,750 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00436% 70/1,605,998 alleles · very rare exomes 61/1,453,840 · genomes 9/152,158 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0314%	3,184
African / African-Americangrpmax	0.00936%	10,679
South Asian	0.00781%	12,796
European (non-Finnish)	0.00289%	34,603
East Asian	0.00224%	44,548
Remaining individualsnot grpmax-eligible	0.00161%	62,192

Finnish 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: DDR2
Protein: p.Ser504=
Coding: c.1512C>T
MANE Select: NM_006182
dbSNP: rs199900233
Type: single nucleotide variant
Location: chr1:162772031 (GRCh38)
Gene constraint: LOEUF 0.375 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.57 · 5 PDB

Full DDR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDR2 p.Ser504Arg Uncertain significance ★★ ⚠ same residue
DDR2 p.Arg341Ter Pathogenic/Likely pathogenic ★★ same type
DDR2 p.Arg611Ter Pathogenic/Likely pathogenic ★★ same type
DDR2 p.Arg752Cys Likely pathogenic ★★ same type
DDR2 p.Leu610Pro Pathogenic/Likely pathogenic ★★ same type
DDR2 c.1728+6T>C Uncertain significance ★★ same type
DDR2 c.-27-11G>C Uncertain significance ★★ same type
DDR2 c.*48A>G 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/ddr2-p-ser504 (accessed [today's date]).

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