Is CARMIL2 p.Lys1237Thr (c.3710A>C) pathogenic?

CARMIL2 p.Lys1237Thr (c.3710A>C) is classified Uncertain significance in CARMIL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-19). AlphaMissense: likely pathogenic (0.8062); Absent from gnomAD v4.1.

How common is CARMIL2 p.Lys1237Thr (c.3710A>C) in the general population?

CARMIL2 p.Lys1237Thr (c.3710A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CARMIL2 p.Lys1237Thr (c.3710A>C)?

AlphaMissense predicts likely pathogenic (score 0.8062) — an in-silico prediction, not a clinical call.

CARMIL2 p.Lys1237Thr

c.3710A>C · rs2142955311 · VCV1400354

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8062 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8062	likely pathogenic
REVEL	0.15	moderately benign-leaning
SaProt	LLR -6.44	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 9.3	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 6,261 bp · p 0.004 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

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.Lys1237Thr
Coding: c.3710A>C
MANE Select: NM_001013838
dbSNP: rs2142955311
Type: single nucleotide variant
Location: chr16:67656035 (GRCh38)
Gene constraint: LOEUF 0.701 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.50
Residue 1237: the 'disordered' region; a UniProt-annotated variant site (in imd58; no detectable protein expression in patient's leukocytes; no effect on homodimerization)

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-lys1237thr (accessed [today's date]).

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