Is LCT p.Phe1449= (c.4347T>C) pathogenic?

LCT p.Phe1449= (c.4347T>C) is classified Benign/Likely benign in LCT (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-04-01). Low-frequency (popmax 1.7%, mid); Associated with congenital lactase deficiency.

What condition is associated with LCT p.Phe1449= (c.4347T>C)?

LCT p.Phe1449= (c.4347T>C) is associated with congenital lactase deficiency (ClinVar).

How common is LCT p.Phe1449= (c.4347T>C) in the general population?

LCT p.Phe1449= (c.4347T>C) is low-frequency (popmax 1.7%, mid) (gnomAD).

How is Congenital lactase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

LCT p.Phe1449=

c.4347T>C · rs17699796 · VCV331175

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.7%, mid)

Conditions

congenital lactase deficiency

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 -0.008	GERP -3.6, phastCons 0.06
Overall
CADD	5.245	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.7% Middle Eastern · 103/6,058 alleles

Filtering AF 1.43% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.33%

Overall 0.785% 12,671/1,614,182 alleles · low-frequency exomes 11,485/1,461,876 · genomes 1,186/152,306 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.88%	53
Middle Easterngrpmax	1.7%	59
Ashkenazi Jewishnot grpmax-eligible	1.22%	82
Remaining individualsnot grpmax-eligible	0.798%	125
European (non-Finnish)	0.792%	126
South Asian	0.779%	128
Admixed American	0.596%	168
African / African-American	0.123%	816
East Asian	0.00223%	44,878

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: LCT
Protein: p.Phe1449=
Coding: c.4347T>C
MANE Select: NM_002299
dbSNP: rs17699796
Type: single nucleotide variant
Location: chr2:135804884 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.63
Residue 1449: the 'glycosyl hydrolase-1 4; region iv. lactase activity' region

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

Disease context

congenital lactase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital lactase deficiency (Orphanet):

Inheritance: Autosomal recessive

Similar variants

LCT c.4866+2T>G Likely pathogenic ★★ same condition
LCT p.Gln1179Ter Pathogenic/Likely pathogenic ★★ same condition
LCT p.Tyr1390Ter Pathogenic ★★ same condition
LCT c.4173+5G>A Uncertain significance ★★ same condition
LCT p.Ala94Thr Uncertain significance ★★ ⚠ same condition
LCT p.Gln594Glu Uncertain significance ★★ ⚠ same condition
LCT p.Gly1400Ser Uncertain significance ★★ ⚠ same condition
LCT p.Gly215Arg Uncertain significance ★★ ⚠ 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/lct-p-phe1449 (accessed [today's date]).

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