Is DDR1 p.Arg63Ser (c.189G>C) pathogenic?

DDR1 p.Arg63Ser (c.189G>C) is classified Uncertain significance in DDR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-17). AlphaMissense: likely pathogenic (0.9953); Very rare (popmax 0.00267%, afr).

How common is DDR1 p.Arg63Ser (c.189G>C) in the general population?

DDR1 p.Arg63Ser (c.189G>C) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about DDR1 p.Arg63Ser (c.189G>C)?

AlphaMissense predicts likely pathogenic (score 0.9953) — an in-silico prediction, not a clinical call.

DDR1 p.Arg63Ser

c.189G>C · VCV4238481

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9953 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9953	likely pathogenic · top 8% in DDR1
REVEL	0.933	strongly pathogenic-leaning
SaProt	LLR -13.99	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.37	acceptor gain · deltas
Pangolin	Δ0.37	loss · gain 0.36 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 8.4	GERP 1.2, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 11 kb · p 3.1e-14 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,940 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,612,926 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: DDR1
Protein: p.Arg63Ser
Coding: c.189G>C
MANE Select: NM_001297654
Type: single nucleotide variant
Location: chr6:30889202 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.27 · 36 PDB
Residue 63: a disulfide bond; the f5/8 type c domain

Full DDR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDR1 p.Ala196Ser Uncertain significance ★ ⚠ same type
DDR1 p.Ala29Val Uncertain significance ★ ⚠ same type
DDR1 p.Ala353Val Uncertain significance ★ ⚠ same type
DDR1 p.Ala383Pro Uncertain significance ★ ⚠ same type
DDR1 p.Ala383Val Uncertain significance ★ ⚠ same type
DDR1 p.Ala521Thr Uncertain significance ★ ⚠ same type
DDR1 p.Ala823Gly Uncertain significance ★ ⚠ same type
DDR1 p.Ala828Ser 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/ddr1-p-arg63ser (accessed [today's date]).

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