Is LCT p.Ser30Phe (c.89C>T) pathogenic?

LCT p.Ser30Phe (c.89C>T) is classified Uncertain significance in LCT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-05). AlphaMissense: likely benign (0.1373); Ultra-rare (popmax 0.0329%, mid); Associated with congenital lactase deficiency.

What condition is associated with LCT p.Ser30Phe (c.89C>T)?

LCT p.Ser30Phe (c.89C>T) is associated with congenital lactase deficiency (ClinVar).

How common is LCT p.Ser30Phe (c.89C>T) in the general population?

LCT p.Ser30Phe (c.89C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

How is Congenital lactase deficiency inherited?

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

What do computational predictors say about LCT p.Ser30Phe (c.89C>T)?

AlphaMissense predicts likely benign (score 0.1373) — an in-silico prediction, not a clinical call.

LCT p.Ser30Phe

c.89C>T · rs368308800 · VCV894535

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1373 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital lactase deficiency

Computational evidence

Protein change
AlphaMissense	0.1373	likely benign
REVEL	0.155	moderately benign-leaning
SaProt	LLR -4.30	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 1.4	GERP -0.007, phastCons 0.094
Regional constraint	o/e 0.89	unconstrained · MANE · 19 kb · p 0.02 · regional, not allelic
Overall
CADD	6.178	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.00851% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00795%

Overall 0.00799% 129/1,613,898 alleles · ultra-rare exomes 124/1,461,792 · genomes 5/152,106 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
European (non-Finnish)	0.01%	10,000
Admixed American	0.00667%	14,997
South Asian	0.00329%	30,360
Remaining individualsnot grpmax-eligible	0.0016%	62,482
African / African-American	0.00134%	74,898

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.Ser30Phe
Coding: c.89C>T
MANE Select: NM_002299
dbSNP: rs368308800
Type: single nucleotide variant
Location: chr2:135837081 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.63

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-ser30phe (accessed [today's date]).

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