Is DRICH1 p.Arg211Trp (c.631C>T) pathogenic?

DRICH1 p.Arg211Trp (c.631C>T) is classified Uncertain significance in DRICH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely benign (0.1219); Ultra-rare (popmax 0.0188%, afr).

How common is DRICH1 p.Arg211Trp (c.631C>T) in the general population?

DRICH1 p.Arg211Trp (c.631C>T) is ultra-rare (popmax 0.0188%, afr) (gnomAD).

What do computational predictors say about DRICH1 p.Arg211Trp (c.631C>T)?

AlphaMissense predicts likely benign (score 0.1219) — an in-silico prediction, not a clinical call.

DRICH1 p.Arg211Trp

c.631C>T · VCV4662174

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1219 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0188%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1219	likely benign
REVEL	0.176	moderately benign-leaning
SaProt	LLR -8.64	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.23	donor loss · deltas
Constraint at this position
Conservation	phyloP -2.6	GERP -2
Regional constraint	o/e 1.03	unconstrained · MANE · 23 kb · p 0.6 · regional, not allelic
Overall
CADD	1.312	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0188% African / African-American · 14/74,616 alleles

Filtering AF 0.0113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00908%

Overall 0.00193% 31/1,603,638 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0188%	5,330
Admixed American	0.00337%	29,676
Remaining individualsnot grpmax-eligible	0.00161%	62,124
European (non-Finnish)	0.00111%	90,136
South Asian	0.0011%	90,688

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: DRICH1
Protein: p.Arg211Trp
Coding: c.631C>T
MANE Select: NM_016449
Type: single nucleotide variant
Location: chr22:23613651 (GRCh38)
Gene constraint: LOEUF 1.309 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.91

Full DRICH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRICH1 p.Arg211Gln Uncertain significance ★ ⚠ same residue
DRICH1 p.Ala21Thr Uncertain significance ★ ⚠ same type
DRICH1 p.Arg133Cys Uncertain significance ★ ⚠ same type
DRICH1 p.Arg159Gln Uncertain significance ★ ⚠ same type
DRICH1 p.Arg75Cys Uncertain significance ★ ⚠ same type
DRICH1 p.Arg75His Uncertain significance ★ ⚠ same type
DRICH1 p.Asp125Ala Uncertain significance ★ ⚠ same type
DRICH1 p.Asp197Tyr 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/drich1-p-arg211trp (accessed [today's date]).

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