Is DIP2C p.Val841Met (c.2521G>A) pathogenic?

DIP2C p.Val841Met (c.2521G>A) is classified Uncertain significance in DIP2C (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-08). AlphaMissense: likely pathogenic (0.5939); Ultra-rare (popmax 0.0209%, sas); Associated with Inborn genetic diseases.

What condition is associated with DIP2C p.Val841Met (c.2521G>A)?

DIP2C p.Val841Met (c.2521G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DIP2C p.Val841Met (c.2521G>A) in the general population?

DIP2C p.Val841Met (c.2521G>A) is ultra-rare (popmax 0.0209%, sas) (gnomAD).

What do computational predictors say about DIP2C p.Val841Met (c.2521G>A)?

AlphaMissense predicts likely pathogenic (score 0.5939) — an in-silico prediction, not a clinical call.

DIP2C p.Val841Met

c.2521G>A · rs753413734 · VCV1920039

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.5939 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5939	likely pathogenic
REVEL	0.333	indeterminate
SaProt	LLR -11.77	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 54 kb · p 2.7e-23 · regional, not allelic
Overall
CADD	26.0	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 0.0209% South Asian · 19/91,060 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.00205% 33/1,613,184 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0209%	4,793
African / African-American	0.00134%	74,902
European (non-Finnish)	0.0011%	90,770

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: DIP2C
Protein: p.Val841Met
Coding: c.2521G>A
MANE Select: NM_014974
dbSNP: rs753413734
Type: single nucleotide variant
Location: chr10:363268 (GRCh38)
Gene constraint: LOEUF 0.235 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.64

Full DIP2C 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

DIP2C p.Val841Ala Uncertain significance ★★ ⚠ same residue
DIP2C p.Ala1066Val Uncertain significance ★★ ⚠ same condition
DIP2C p.Ala1101Val Uncertain significance ★★ ⚠ same condition
DIP2C p.Ala1155Thr Uncertain significance ★★ ⚠ same condition
DIP2C p.Ala1466Thr Uncertain significance ★★ ⚠ same condition
DIP2C p.Ala193Val Uncertain significance ★★ ⚠ same condition
DIP2C p.Ala422Thr Uncertain significance ★★ ⚠ same condition
DIP2C p.Ala71Thr 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/dip2c-p-val841met (accessed [today's date]).

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