Is LITAF p.Phe136Leu (c.408C>A) pathogenic?

LITAF p.Phe136Leu (c.408C>A) is classified Uncertain significance in LITAF (ClinVar, Single submitter, 1 submitter; last evaluated 2016-12-22). AlphaMissense: likely pathogenic (0.9703); Absent from gnomAD v4.1.

How common is LITAF p.Phe136Leu (c.408C>A) in the general population?

LITAF p.Phe136Leu (c.408C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LITAF p.Phe136Leu (c.408C>A)?

AlphaMissense predicts likely pathogenic (score 0.9703) — an in-silico prediction, not a clinical call.

LITAF p.Phe136Leu

c.408C>A · rs1057524422 · VCV392274

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9703 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9703	likely pathogenic · top 10% in LITAF
REVEL	0.586	indeterminate
SaProt	LLR -10.47	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 0.015, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 7,090 bp · p 0.61 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Phe136Leu
Coding: c.408C>A
MANE Select: NM_001136472
dbSNP: rs1057524422
Type: single nucleotide variant
Location: chr16:11549715 (GRCh38)
Gene constraint: LOEUF 1.017 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 70.60
Residue 136: the litaf domain

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

Similar variants

LITAF p.Phe136Ser Uncertain significance ★ ⚠ same residue
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

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-phe136leu (accessed [today's date]).

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