Is CLMN p.Val489Phe (c.1465G>T) pathogenic?

CLMN p.Val489Phe (c.1465G>T) is classified Benign in CLMN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0888); Common (popmax 5.48%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CLMN p.Val489Phe (c.1465G>T)?

AlphaMissense predicts likely benign (score 0.0888) — an in-silico prediction, not a clinical call.

CLMN p.Val489Phe

Q: How common is CLMN p.Val489Phe (c.1465G>T) in the general population?

CLMN p.Val489Phe (c.1465G>T) is common (popmax 5.48%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1465G>T · rs116654567 · VCV783697

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0888 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.48%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0888	likely benign
REVEL	0.304	indeterminate
SaProt	LLR -7.96	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 -0.47	GERP -3.6
Regional constraint	o/e 0.94	unconstrained · MANE · 128 kb · p 0.024 · regional, not allelic
Overall
CADD	8.597	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

Grpmax group 5.48% African / African-American · 4,114/75,034 alleles

Filtering AF 5.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.29%

Overall 0.291% 4,699/1,614,146 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.48%	18
Remaining individualsnot grpmax-eligible	0.373%	268
Admixed American	0.353%	283
Middle Eastern	0.214%	466
European (non-Finnish)	0.0101%	9,916
South Asian	0.00878%	11,385

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: CLMN
Protein: p.Val489Phe
Coding: c.1465G>T
MANE Select: NM_024734
dbSNP: rs116654567
Type: single nucleotide variant
Location: chr14:95203884 (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-val489phe (accessed [today's date]).

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