Is CARMIL2 p.Arg121Pro (c.362G>C) pathogenic?

CARMIL2 p.Arg121Pro (c.362G>C) is classified Uncertain significance in CARMIL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-29). AlphaMissense: likely benign (0.1993); Absent from gnomAD v4.1.

How common is CARMIL2 p.Arg121Pro (c.362G>C) in the general population?

CARMIL2 p.Arg121Pro (c.362G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CARMIL2 p.Arg121Pro (c.362G>C)?

AlphaMissense predicts likely benign (score 0.1993) — an in-silico prediction, not a clinical call.

CARMIL2 p.Arg121Pro

c.362G>C · rs755572102 · VCV1469969

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1993 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1993	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -8.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.31	donor gain · deltas
Pangolin	Δ0.25	gain · loss 0.06 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.9	GERP -3.4, phastCons 0.96
Regional constraint	o/e 0.97	unconstrained · MANE · 4,899 bp · p 0.31 · regional, not allelic
Overall
CADD	15.88	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CARMIL2
Protein: p.Arg121Pro
Coding: c.362G>C
MANE Select: NM_001013838
dbSNP: rs755572102
Type: single nucleotide variant
Location: chr16:67646298 (GRCh38)
Gene constraint: LOEUF 0.701 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.50

Full CARMIL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CARMIL2 c.1334+1G>T Likely pathogenic ★★ same type
CARMIL2 c.2313+1G>A Likely pathogenic ★★ same type
CARMIL2 c.871+1G>T Pathogenic ★★ same type
CARMIL2 c.958+1G>A Likely pathogenic ★★ same type
CARMIL2 p.Arg174Ter Pathogenic/Likely pathogenic ★★ same type
CARMIL2 p.Asn530Lys Pathogenic/Likely pathogenic ★★ same type
CARMIL2 p.Gln1379Ter Pathogenic/Likely pathogenic ★★ same type
CARMIL2 p.Ser370Ter 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/carmil2-p-arg121pro (accessed [today's date]).

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