Is LCT p.Phe71Ser (c.212T>C) pathogenic?

LCT p.Phe71Ser (c.212T>C) is classified Uncertain significance in LCT (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-23). AlphaMissense: likely benign (0.1366); Very rare (popmax 0.00133%, afr).

How common is LCT p.Phe71Ser (c.212T>C) in the general population?

LCT p.Phe71Ser (c.212T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about LCT p.Phe71Ser (c.212T>C)?

AlphaMissense predicts likely benign (score 0.1366) — an in-silico prediction, not a clinical call.

LCT p.Phe71Ser

c.212T>C · VCV4956797

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1366 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1366	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -8.07	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 0.07	GERP -3.5
Regional constraint	o/e 0.89	unconstrained · MANE · 19 kb · p 0.02 · regional, not allelic
Overall
CADD	5.173	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 0.00133% African / African-American · 1/75,034 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,614,154 alleles · very rare exomes 4/1,461,876 · genomes 0/152,278 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,034
European (non-Finnish)	0.000254%	393,335

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.Phe71Ser
Coding: c.212T>C
MANE Select: NM_002299
Type: single nucleotide variant
Location: chr2:135836958 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.63
Residue 71: the 'glycosyl hydrolase-1 1; region i' region

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

Similar variants

LCT p.Phe71Tyr Uncertain significance ★★ ⚠ same residue
LCT p.Phe71fs Pathogenic ★ same residue
LCT c.4866+2T>G Likely pathogenic ★★ same type
LCT p.Gln1179Ter Pathogenic/Likely pathogenic ★★ same type
LCT p.Lys787Ter Pathogenic/Likely pathogenic ★★ same type
LCT p.Tyr1390Ter Pathogenic ★★ same type
LCT c.4173+5G>A Uncertain significance ★★ same type
LCT p.Ala1398Glu Uncertain significance ★★ ⚠ 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/lct-p-phe71ser (accessed [today's date]).

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