Is CLMN p.Asp166Asn (c.496G>A) pathogenic?

CLMN p.Asp166Asn (c.496G>A) is classified Uncertain significance in CLMN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely benign (0.3238); Absent from gnomAD v4.1.

How common is CLMN p.Asp166Asn (c.496G>A) in the general population?

CLMN p.Asp166Asn (c.496G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLMN p.Asp166Asn (c.496G>A)?

AlphaMissense predicts likely benign (score 0.3238) — an in-silico prediction, not a clinical call.

CLMN p.Asp166Asn

c.496G>A · rs2543920351 · VCV2608875

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3238 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3238	likely benign
REVEL	0.383	indeterminate
SaProt	LLR -7.62	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 128 kb · p 0.024 · regional, not allelic
Overall
CADD	29.6	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: CLMN
Protein: p.Asp166Asn
Coding: c.496G>A
MANE Select: NM_024734
dbSNP: rs2543920351
Type: single nucleotide variant
Location: chr14:95213331 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.84
Residue 166: the 'actin-binding' region; the 'disordered' region

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

Similar variants

CLMN c.2511+10C>T Benign ★★ same type
CLMN c.886-4G>T Likely benign ★★ same type
CLMN p.Asp592= Benign ★★ same type
CLMN p.Glu276Lys Likely benign ★★ same type
CLMN p.Glu357Lys Benign ★★ same type
CLMN p.Glu771Ala Likely benign ★★ ⚠ same type
CLMN p.His518= Benign ★★ same type
CLMN p.Ile900Phe Benign ★★ 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/clmn-p-asp166asn (accessed [today's date]).

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