Is LITAF p.Pro41Ser (c.121C>T) pathogenic?

LITAF p.Pro41Ser (c.121C>T) is classified Uncertain significance in LITAF (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-02). AlphaMissense: likely benign (0.096); Absent from gnomAD v4.1.

How common is LITAF p.Pro41Ser (c.121C>T) in the general population?

LITAF p.Pro41Ser (c.121C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LITAF p.Pro41Ser (c.121C>T)?

AlphaMissense predicts likely benign (score 0.096) — an in-silico prediction, not a clinical call.

LITAF p.Pro41Ser

c.121C>T · VCV4976031

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.096 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.096	likely benign
REVEL	0.378	indeterminate
SaProt	LLR -6.75	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	GERP 0.74, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 7,090 bp · p 0.61 · regional, not allelic
Overall
CADD	25.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LITAF
Protein: p.Pro41Ser
Coding: c.121C>T
MANE Select: NM_001136472
Type: single nucleotide variant
Location: chr16:11556610 (GRCh38)
Gene constraint: LOEUF 1.017 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 70.60

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

Similar variants

LITAF p.Ala111Gly Pathogenic ★★ same type
LITAF p.Gly112Ser Pathogenic ★★ ⚠ same type
LITAF p.Thr115Asn Pathogenic/Likely pathogenic ★★ same type
LITAF c.220+4C>T Uncertain significance ★★ same type
LITAF p.Ala129Val Uncertain significance ★★ ⚠ same type
LITAF p.Ala140Thr Uncertain significance ★★ ⚠ same type
LITAF p.Ala153Thr Uncertain significance ★★ ⚠ same type
LITAF p.Ala153Val 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/litaf-p-pro41ser (accessed [today's date]).

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