Is RANBP2 p.Pro2247Ser (c.6739C>T) pathogenic?

RANBP2 p.Pro2247Ser (c.6739C>T) is classified Conflicting classifications of pathogenicity in RANBP2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-03-01). AlphaMissense: likely benign (0.2478); Rare (popmax 0.183%, afr).

How common is RANBP2 p.Pro2247Ser (c.6739C>T) in the general population?

RANBP2 p.Pro2247Ser (c.6739C>T) is rare (popmax 0.183%, afr) (gnomAD).

What do computational predictors say about RANBP2 p.Pro2247Ser (c.6739C>T)?

AlphaMissense predicts likely benign (score 0.2478) — an in-silico prediction, not a clinical call.

RANBP2 p.Pro2247Ser

c.6739C>T · rs141067955 · VCV2339428

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2478 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.183%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.2478	likely benign
REVEL	0.169	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 225 bp · p 0.11 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.183% African / African-American · 137/74,984 alleles

Filtering AF 0.158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.148%

Overall 0.00937% 151/1,612,054 alleles · rare exomes 78/1,459,710 · genomes 73/152,344 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.183%	547
Admixed American	0.0133%	7,502
Remaining individualsnot grpmax-eligible	0.00802%	12,464
European (non-Finnish)	8.48e-05%	1,179,862

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: RANBP2
Protein: p.Pro2247Ser
Coding: c.6739C>T
MANE Select: NM_006267
dbSNP: rs141067955
Type: single nucleotide variant
Location: chr2:108767278 (GRCh38)
Gene constraint: LOEUF 0.231 · pLI 1.00 (gnomAD)
Residue 2247: the '22 x 2 aa repeats of f-g' region; the 'interaction with bicd2' region

Full RANBP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EDAR p.Arg358Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
RANBP2 p.Thr585Met Pathogenic/Likely pathogenic ★★ ⚠ same type
EDAR p.Leu353Phe Uncertain significance ★★ ⚠ same type
RANBP2 c.406-2A>G Uncertain significance ★★ same type
RANBP2 p.Ala2337Val Uncertain significance ★★ same type
RANBP2 p.Ala2564Ser Uncertain significance ★★ ⚠ same type
RANBP2 p.Ala3072Val Uncertain significance ★★ ⚠ same type
RANBP2 p.Ala534Val 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/ranbp2-p-pro2247ser (accessed [today's date]).

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