Is SFTPC p.Leu101= (c.303C>T) pathogenic?

SFTPC p.Leu101= (c.303C>T) is classified Benign in SFTPC (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Very rare (popmax 0.00669%, eas); Associated with interstitial lung disease 2.

What condition is associated with SFTPC p.Leu101= (c.303C>T)?

SFTPC p.Leu101= (c.303C>T) is associated with interstitial lung disease 2, surfactant metabolism dysfunction, pulmonary, 2 (ClinVar).

How common is SFTPC p.Leu101= (c.303C>T) in the general population?

SFTPC p.Leu101= (c.303C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

SFTPC p.Leu101=

c.303C>T · rs370825102 · VCV908426

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Conditions

interstitial lung disease 2

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 -9.9	GERP -3.1
Overall
CADD	1.658	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,876 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000558% 9/1,614,174 alleles · very rare exomes 9/1,461,868 · genomes 0/152,306 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,959
Admixed American	0.005%	20,009
South Asian	0.0011%	91,070
European (non-Finnish)	0.000169%	590,016

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: SFTPC
Protein: p.Leu101=
Coding: c.303C>T
MANE Select: NM_001317778
dbSNP: rs370825102
Type: single nucleotide variant
Location: chr8:22163181 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.71 · 3 PDB
Residue 101: a β-strand; the brichos domain

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

Disease context

interstitial lung disease 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: surfactant metabolism dysfunction, pulmonary, 2

Similar variants

SFTPC c.435+2T>C Pathogenic/Likely pathogenic ★★ same condition
SFTPC p.Ile73Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
SFTPC c.*193C>A Uncertain significance ★★ same condition
SFTPC p.Ile50Met Uncertain significance ★★ ⚠ same condition
SFTPC p.Leu45Pro Uncertain significance ★★ ⚠ same condition
SFTPC p.Val39Met Uncertain significance ★★ ⚠ same condition
SFTPC c.201+14G>A Benign/Likely benign ★★ same condition
SFTPC c.201+49C>A Benign ★★ same condition

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/sftpc-p-leu101 (accessed [today's date]).

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