Is REN p.Asp211Asn (c.631G>A) pathogenic?

REN p.Asp211Asn (c.631G>A) is classified Uncertain significance in REN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-24). AlphaMissense: ambiguous (0.3955); Very rare (popmax 0.000593%, nfe); Associated with REN-related disorder.

What condition is associated with REN p.Asp211Asn (c.631G>A)?

REN p.Asp211Asn (c.631G>A) is associated with REN-related disorder (ClinVar).

How common is REN p.Asp211Asn (c.631G>A) in the general population?

REN p.Asp211Asn (c.631G>A) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about REN p.Asp211Asn (c.631G>A)?

AlphaMissense predicts ambiguous (score 0.3955) — an in-silico prediction, not a clinical call.

REN p.Asp211Asn

c.631G>A · rs764665629 · VCV2216306

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3955 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Conditions

REN-related disorder

Computational evidence

Protein change
AlphaMissense	0.3955	ambiguous
REVEL	0.408	indeterminate
SaProt	LLR -9.16	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.2, phastCons 1
Overall
CADD	26.9	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 0.000593% European (non-Finnish) · 7/1,180,026 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000616% 9/1,461,890 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,253
European (non-Finnish)grpmax	0.000593%	168,575

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: REN
Protein: p.Asp211Asn
Coding: c.631G>A
MANE Select: NM_001363642 · reported on NM_000537
dbSNP: rs764665629
Type: single nucleotide variant
Location: chr1:204159457 (GRCh38)
Structure: AlphaFold pLDDT 85.00

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

Disease context

REN-related disorder

Similar variants

REN c.961-5C>A Conflicting classifications of pathogenicity ★ same condition
REN p.Thr122Ala Uncertain significance ⚠ same condition
REN c.689+7A>G Likely benign same condition
REN p.Lys37= Likely benign same condition
REN p.Ile262fs Likely pathogenic ★ same condition
REN c.250-5dup Likely benign same condition
REN c.249+1G>A Pathogenic/Likely pathogenic ★★ same type
REN p.Arg49Ter Pathogenic/Likely pathogenic ★★ 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/ren-p-asp211asn (accessed [today's date]).

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