Is CLCF1 p.Asp183= (c.549C>T) pathogenic?

CLCF1 p.Asp183= (c.549C>T) is classified Likely benign in CLCF1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-25). Ultra-rare (popmax 0.0329%, sas); Associated with CLCF1-related disorder.

What condition is associated with CLCF1 p.Asp183= (c.549C>T)?

CLCF1 p.Asp183= (c.549C>T) is associated with CLCF1-related disorder (ClinVar).

How common is CLCF1 p.Asp183= (c.549C>T) in the general population?

CLCF1 p.Asp183= (c.549C>T) is ultra-rare (popmax 0.0329%, sas) (gnomAD).

CLCF1 p.Asp183=

c.549C>T · rs767970190 · VCV3039157

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, sas)

Conditions

CLCF1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.8	GERP -4
Overall
CADD	3.088	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% South Asian · 30/91,086 alleles

Filtering AF 0.0237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0205%

Overall 0.00235% 38/1,614,004 alleles · ultra-rare exomes 36/1,461,676 · genomes 2/152,328 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0329%	3,036
East Asian	0.00891%	11,222
Admixed American	0.00167%	60,032
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)	0.000169%	590,019

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: CLCF1
Protein: p.Asp183=
Coding: c.549C>T
MANE Select: NM_013246
dbSNP: rs767970190
Type: single nucleotide variant
Location: chr11:67365265 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI 0.33 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.59 · 2 PDB
Residue 183: an α-helix

Full CLCF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CLCF1-related disorder

Similar variants

CLCF1 p.Val25= Likely benign same condition
CLCF1 p.Arg122His Uncertain significance ★★ ⚠ same type
CLCF1 p.Arg130His Uncertain significance ★★ ⚠ same type
CLCF1 p.Arg30His Uncertain significance ★★ ⚠ same type
CLCF1 p.Pro38Ser Uncertain significance ★★ ⚠ same type
CLCF1 p.Ser198Leu Uncertain significance ★★ ⚠ same type
CLC p.Asn65Lys Benign ★★ ⚠ same type
CLCF1 c.183+14G>A 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/clcf1-p-asp183 (accessed [today's date]).

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