Is MORC2 p.Ile647Val (c.1939A>G) pathogenic?

MORC2 p.Ile647Val (c.1939A>G) is classified Uncertain significance in MORC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-04). AlphaMissense: likely benign (0.0694); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with MORC2 p.Ile647Val (c.1939A>G)?

MORC2 p.Ile647Val (c.1939A>G) is associated with Inborn genetic diseases (ClinVar).

How common is MORC2 p.Ile647Val (c.1939A>G) in the general population?

MORC2 p.Ile647Val (c.1939A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about MORC2 p.Ile647Val (c.1939A>G)?

AlphaMissense predicts likely benign (score 0.0694) — an in-silico prediction, not a clinical call.

MORC2 p.Ile647Val

c.1939A>G · rs1477506756 · VCV1783011

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0694 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0694	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -5.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.8	GERP -0.87
Regional constraint	o/e 1.02	unconstrained · MANE · 1,093 bp · p 0.79 · regional, not allelic
Overall
CADD	0.292	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 0.00267% African / African-American · 2/74,846 alleles

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

Overall 0.000186% 3/1,613,900 alleles · very rare exomes 2/1,461,876 · genomes 1/152,024 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,423
East Asian	0.00223%	44,874

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: MORC2
Protein: p.Ile647Val
Coding: c.1939A>G
MANE Select: NM_001303256
dbSNP: rs1477506756
Type: single nucleotide variant
Location: chr22:30935035 (GRCh38)
Gene constraint: LOEUF 0.3 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.37 · 9 PDB
Residue 647: the 'disordered' region

Full MORC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MORC2 p.Ile647Thr Likely benign ★ same residue
MORC2 p.Tyr394Cys Pathogenic/Likely pathogenic ★★ same condition
MORC2 c.68+4A>C Uncertain significance ★★ same condition
MORC2 p.Ala448Val Uncertain significance ★★ ⚠ same condition
MORC2 p.Ala741Thr Uncertain significance ★★ ⚠ same condition
MORC2 p.Arg287Cys Uncertain significance ★★ ⚠ same condition
MORC2 p.Arg535Trp Uncertain significance ★★ ⚠ same condition
MORC2 p.Arg608His Uncertain significance ★★ ⚠ same condition

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/morc2-p-ile647val (accessed [today's date]).

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