Is CFC1 p.Phe162Leu (c.484T>C) pathogenic?

CFC1 p.Phe162Leu (c.484T>C) is classified Benign in CFC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-28). AlphaMissense: likely pathogenic (0.6938); Low-frequency (popmax 2.08%, afr); Associated with heterotaxy, visceral, 2, autosomal.

What condition is associated with CFC1 p.Phe162Leu (c.484T>C)?

CFC1 p.Phe162Leu (c.484T>C) is associated with heterotaxy, visceral, 2, autosomal (ClinVar).

How common is CFC1 p.Phe162Leu (c.484T>C) in the general population?

CFC1 p.Phe162Leu (c.484T>C) is low-frequency (popmax 2.08%, afr) (gnomAD).

What do computational predictors say about CFC1 p.Phe162Leu (c.484T>C)?

AlphaMissense predicts likely pathogenic (score 0.6938) — an in-silico prediction, not a clinical call.

CFC1 p.Phe162Leu

c.484T>C · rs776829911 · VCV801752

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6938 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.08%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

heterotaxy, visceral, 2, autosomal

Computational evidence

Protein change
AlphaMissense	0.6938	likely pathogenic
REVEL	0.509	indeterminate
SaProt	LLR -4.01	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.16
Regional constraint	o/e 0.12	constrained · MANE · 6,407 bp · p 3.7e-22 · regional, not allelic
Overall
CADD	13.73	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 2.08% African / African-American · 884/42,434 alleles

Filtering AF 1.97% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.92%

Overall 0.192% 1,034/539,018 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.08%	48
Admixed American	0.226%	442
Remaining individualsnot grpmax-eligible	0.193%	518
Middle Eastern	0.095%	1,053
South Asian	0.0126%	7,967
European (non-Finnish)	0.00778%	12,859
Ashkenazi Jewishnot grpmax-eligible	0.00626%	15,974

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: CFC1
Protein: p.Phe162Leu
Coding: c.484T>C
MANE Select: NM_032545
dbSNP: rs776829911
Type: single nucleotide variant
Location: chr2:130593065 (GRCh38)
Gene constraint: LOEUF 0.586 · pLI 0.86 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.18

Full CFC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

heterotaxy, visceral, 2, autosomal — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFC1 p.Ala145Thr Benign ★★ same condition
CFC1 p.Arg28Lys Uncertain significance ★ ⚠ same condition
CFC1 p.Arg112Cys Pathogenic same condition
CFC1 p.Glu66fs Likely pathogenic ★ same condition
CFC1 p.Ala175fs Conflicting classifications of pathogenicity ★ same condition
CFC1 c.361_362+18dup Pathogenic same condition
CFC1 p.Gly33Ser Uncertain significance ★★ ⚠ same type
CFC1 p.Arg47Gln 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/cfc1-p-phe162leu (accessed [today's date]).

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