Is CARMIL2 p.Arg385Ser (c.1155G>T) pathogenic?

CARMIL2 p.Arg385Ser (c.1155G>T) is classified Uncertain significance in CARMIL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-24). AlphaMissense: likely benign (0.2329); Very rare (popmax 0.000509%, nfe).

How common is CARMIL2 p.Arg385Ser (c.1155G>T) in the general population?

CARMIL2 p.Arg385Ser (c.1155G>T) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about CARMIL2 p.Arg385Ser (c.1155G>T)?

AlphaMissense predicts likely benign (score 0.2329) — an in-silico prediction, not a clinical call.

CARMIL2 p.Arg385Ser

c.1155G>T · rs754658699 · VCV1375101

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2329 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2329	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -5.68	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.42	donor gain · deltas
Pangolin	Δ0.43	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.2	GERP -1.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 4,899 bp · p 0.31 · regional, not allelic
Overall
CADD	13.19	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 0.000509% European (non-Finnish) · 6/1,179,552 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,612,808 alleles · very rare exomes 5/1,460,788 · genomes 1/152,020 · joint denominator

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: CARMIL2
Protein: p.Arg385Ser
Coding: c.1155G>T
MANE Select: NM_001013838
dbSNP: rs754658699
Type: single nucleotide variant
Location: chr16:67648135 (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 p.Arg385= Likely benign ★ same residue
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

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-arg385ser (accessed [today's date]).

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