Is CLMN p.Ile900Phe (c.2698A>T) pathogenic?

CLMN p.Ile900Phe (c.2698A>T) is classified Benign in CLMN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1196); Common (popmax 5.16%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CLMN p.Ile900Phe (c.2698A>T)?

AlphaMissense predicts likely benign (score 0.1196) — an in-silico prediction, not a clinical call.

CLMN p.Ile900Phe

Q: How common is CLMN p.Ile900Phe (c.2698A>T) in the general population?

CLMN p.Ile900Phe (c.2698A>T) is common (popmax 5.16%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2698A>T · rs61750771 · VCV776857

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1196 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.16%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1196	likely benign
REVEL	0.24	benign-leaning
SaProt	LLR -5.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.053	GERP -3.1, phastCons 0.002
Regional constraint	o/e 0.94	unconstrained · MANE · 128 kb · p 0.024 · regional, not allelic
Overall
CADD	6.475	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 5.16% African / African-American · 3,844/74,526 alleles

Filtering AF 5.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.97%

Overall 0.272% 4,384/1,609,466 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.16%	19
Middle Eastern	0.481%	208
Remaining individualsnot grpmax-eligible	0.382%	262
Admixed American	0.318%	315
South Asian	0.00779%	12,843
European (non-Finnish)	0.00662%	15,112
Finnishnot grpmax-eligible	0.00156%	63,990

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.Ile900Phe
Coding: c.2698A>T
MANE Select: NM_024734
dbSNP: rs61750771
Type: single nucleotide variant
Location: chr14:95196508 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.84
Residue 900: 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.Leu111= 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-ile900phe (accessed [today's date]).

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