Is CLMN p.Phe573Val (c.1717T>G) pathogenic?

CLMN p.Phe573Val (c.1717T>G) is classified Uncertain significance in CLMN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). AlphaMissense: likely benign (0.176); Absent from gnomAD v4.1.

How common is CLMN p.Phe573Val (c.1717T>G) in the general population?

CLMN p.Phe573Val (c.1717T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLMN p.Phe573Val (c.1717T>G)?

AlphaMissense predicts likely benign (score 0.176) — an in-silico prediction, not a clinical call.

CLMN p.Phe573Val

c.1717T>G · rs2543893894 · VCV2547005

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.176 · 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	0.176	likely benign
REVEL	0.299	indeterminate
SaProt	LLR -6.14	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 128 kb · p 0.024 · regional, not allelic
Overall
CADD	17.97	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.Phe573Val
Coding: c.1717T>G
MANE Select: NM_024734
dbSNP: rs2543893894
Type: single nucleotide variant
Location: chr14:95203632 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.84

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-phe573val (accessed [today's date]).

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